Received: 12/09/2024 Accepted: 16/11/2024 Published: 07/02/2025 1 of 8
https://doi.org/10.52973/rcfcv-e35516 Scientific Journal, FCV-LUZ / Vol. XXXV
ABSTRACT
Sex-related differences were investigated in ultrastructural
modifications that occur with ageing in the rat carotid artery in the
study. As ageing impacts every system and organ within the human
body, it also impacts the circulatory system. The circulatory system
serves various functions in the body such as nourishing organs and
tissues, oxygenating and eliminating toxic substances. A condition
like atherosclerosis or thrombosis in the circulatory system results
in permanent harm to structures like the central nervous system,
heart and even fatality. Although the pathologies observed in the
vessels are commonly attributed to the generation of atheromas,
it has been recognised in recent years that changes in the tunica
intima and tunica media lead to impaired vascular function
without the formation of atheromas. Despite the long-standing
belief that women have a advantage in age-related cardiovascular
diseases, there has been no ultrastructural examination to support
this theory. We explored the sex-related discrepancies in the
ultrastructural modifications produced by aging in the carotid
artery. A total of 28 Sprague-Dawley rats, 14 males and 14 females,
were planned to be used in the study. Of these 28 rats, 4 females
and 4 males was constitute the control group. The rats in the
control group was approximately 10 weeks old, and the rats in
the experimental group, which was represent the aged group,
was 19 weeks old. All animals in the study were anaesthetised
and then sacrificed by removal of the heart. The right and left
common carotid arteries were removed from the sacrificed animals.
Collected vessels prepared for Transmission Electron Microscopy
(TEM) examination. For each animal, at least four TEM images
were taken from four different sections from the same block. As
a result, the impact of vascular ageing manifested as apoptosis
and age-related dysfunction in endothelial cells, thickening of the
subendothelial layer, elastin deterioration, collagen deposition in
the matrix, and degradation of the internal elastic lamina. Notably,
vascular degeneration is more severe in men than in women. It
is clear that the endothelium is subject to accumulated damage
with age. We believe that the dissimilarity between males and
females is attributed to the estrogen’s proliferative and anti-
inflamedry impact.
Key words: Ageing; endothelium; electron microscopy; gender-
dependent difference; ultrastructural
SUMMARY
We investigate sex-related differences in
The ultrastructural modifications that occur with the
Aging in the rat carotid artery. Aging
affects all systems and organs of the human body, and
also to the circulatory system. The circulatory system plays
various functions in the body, such as nourishing organs and tissues,
oxygenate and eliminate toxic substances. A condition such as
atherosclerosis or thrombosis in the circulatory system causes
permanent damage to structures such as the nervous system
central, the heart and even death. Although the pathologies
observed in the vessels are commonly attributed to the generation
of atheromas, in recent years it has been recognized that the changes
in the tunica intima and tunica media lead to deterioration
vascular function without the formation of atheromas. Despite
the deep-rooted belief that women have an advantage in
age-related cardiovascular diseases, it has not been
No ultrastructural examination has been performed to support this theory.
We explore gender-related discrepancies in the
ultrastructural modifications produced by aging
in the carotid artery. A total of 1000 patients were planned to be treated in the study.
28 Sprague-Dawley rats, 14 males and 14 females. Of these 28
rats, 4 females and 4 males will constitute the control group. The
Rats in the control group will be approximately 10 weeks old
of age, and those of the experimental group, which will represent the group
aged, 19 weeks. All animals in the study will be
anesthetized and sacrificed by extracting the heart.
The right and left common carotid arteries were removed
from the sacrificed animals. The extracted vessels were prepared
for TEM examination. For each animal, at least
four TEM images of four different sections of the same
block. As a result, the impact of vascular aging
manifested as apoptosis and dysfunction related to
age in endothelial cells, thickening of the layer
subendothelial, elastin deterioration, collagen deposition in
the matrix and degradation of the internal elastic lamina. In particular,
Vascular degeneration is more severe in men than in women.
women. It is clear that the endothelium suffers cumulative damage with
age. We believe that the difference between men and women is
attributed to the proliferative and anti-inflammatory effect of estrogens.
Keywords: Aging; endothelium; microscopy
electronics; sex-dependent difference;
ultrastructural
Ultrastructural changes in the common carotid artery in terms of age
and gender-related in Rat model
Ultrastructural changes in the common carotid artery in
Function of age and sex in a rat model
Nejat Unlukal
Selcuk University, Faculty of Medicine, Department of Histology and Embryology. Konya, Türkiye.
*Corresponding author: nejatunlukal@gmail.com
https://doi.org/10.52973/rcfcv-e35516 Scientific Journal, FCV-LUZ / Vol. XXXV
ABSTRACT
Sex-related differences were investigated in ultrastructural
modifications that occur with ageing in the rat carotid artery in the
study. As ageing impacts every system and organ within the human
body, it also impacts the circulatory system. The circulatory system
serves various functions in the body such as nourishing organs and
tissues, oxygenating and eliminating toxic substances. A condition
like atherosclerosis or thrombosis in the circulatory system results
in permanent harm to structures like the central nervous system,
heart and even fatality. Although the pathologies observed in the
vessels are commonly attributed to the generation of atheromas,
it has been recognised in recent years that changes in the tunica
intima and tunica media lead to impaired vascular function
without the formation of atheromas. Despite the long-standing
belief that women have a advantage in age-related cardiovascular
diseases, there has been no ultrastructural examination to support
this theory. We explored the sex-related discrepancies in the
ultrastructural modifications produced by aging in the carotid
artery. A total of 28 Sprague-Dawley rats, 14 males and 14 females,
were planned to be used in the study. Of these 28 rats, 4 females
and 4 males was constitute the control group. The rats in the
control group was approximately 10 weeks old, and the rats in
the experimental group, which was represent the aged group,
was 19 weeks old. All animals in the study were anaesthetised
and then sacrificed by removal of the heart. The right and left
common carotid arteries were removed from the sacrificed animals.
Collected vessels prepared for Transmission Electron Microscopy
(TEM) examination. For each animal, at least four TEM images
were taken from four different sections from the same block. As
a result, the impact of vascular ageing manifested as apoptosis
and age-related dysfunction in endothelial cells, thickening of the
subendothelial layer, elastin deterioration, collagen deposition in
the matrix, and degradation of the internal elastic lamina. Notably,
vascular degeneration is more severe in men than in women. It
is clear that the endothelium is subject to accumulated damage
with age. We believe that the dissimilarity between males and
females is attributed to the estrogen’s proliferative and anti-
inflamedry impact.
Key words: Ageing; endothelium; electron microscopy; gender-
dependent difference; ultrastructural
SUMMARY
We investigate sex-related differences in
The ultrastructural modifications that occur with the
Aging in the rat carotid artery. Aging
affects all systems and organs of the human body, and
also to the circulatory system. The circulatory system plays
various functions in the body, such as nourishing organs and tissues,
oxygenate and eliminate toxic substances. A condition such as
atherosclerosis or thrombosis in the circulatory system causes
permanent damage to structures such as the nervous system
central, the heart and even death. Although the pathologies
observed in the vessels are commonly attributed to the generation
of atheromas, in recent years it has been recognized that the changes
in the tunica intima and tunica media lead to deterioration
vascular function without the formation of atheromas. Despite
the deep-rooted belief that women have an advantage in
age-related cardiovascular diseases, it has not been
No ultrastructural examination has been performed to support this theory.
We explore gender-related discrepancies in the
ultrastructural modifications produced by aging
in the carotid artery. A total of 1000 patients were planned to be treated in the study.
28 Sprague-Dawley rats, 14 males and 14 females. Of these 28
rats, 4 females and 4 males will constitute the control group. The
Rats in the control group will be approximately 10 weeks old
of age, and those of the experimental group, which will represent the group
aged, 19 weeks. All animals in the study will be
anesthetized and sacrificed by extracting the heart.
The right and left common carotid arteries were removed
from the sacrificed animals. The extracted vessels were prepared
for TEM examination. For each animal, at least
four TEM images of four different sections of the same
block. As a result, the impact of vascular aging
manifested as apoptosis and dysfunction related to
age in endothelial cells, thickening of the layer
subendothelial, elastin deterioration, collagen deposition in
the matrix and degradation of the internal elastic lamina. In particular,
Vascular degeneration is more severe in men than in women.
women. It is clear that the endothelium suffers cumulative damage with
age. We believe that the difference between men and women is
attributed to the proliferative and anti-inflammatory effect of estrogens.
Keywords: Aging; endothelium; microscopy
electronics; sex-dependent difference;
ultrastructural
Ultrastructural changes in the common carotid artery in terms of age
and gender-related in Rat model
Ultrastructural changes in the common carotid artery in
Function of age and sex in a rat model
Nejat Unlukal
Selcuk University, Faculty of Medicine, Department of Histology and Embryology. Konya, Türkiye.
*Corresponding author: nejatunlukal@gmail.com
Ultrastructural changes in the common carotid artery in Rat model / Ünlükal _______________________________________________________2 of 8
INTRODUCTION
Common carotid arteries are the main arteries supplying the
head region. The right common carotid artery originates from the
arcus aorta and the left side from the brachiocephalic artery [1,
2]. The aorta and its branches are called elastic arteries. Elastic
arteries are responsible for the pulsatile progression of blood
through the vessel. In other words, they enable the blood pumped
by the heart throughout systole to flow during diastole. Elastic
arteries consist of tunica intima, tunica media and tunica adventitia.
The tunica intima comprises endothelium, subendothelial layer,
and internal elastic membrane.
The subendothelial layer contains collagen and elastic fibres
synthesised by smooth muscle cells. The tunica media is the
thickest layer in the elastic arteries and contains abundant layers
of elastic fibres. While the elastic fibre layers in this layer are
few or absent at birth, they gradually increase in number with
advancing age. The tunica adventitia consists of a connective layer
which is considerably thinner than the tunica media. Although
collagen fibres are present in all layers, their ratio in the adventitia
is higher, thus helping to keep the expansion of the vessel wall
within physiological limits during systole [3, 4].
Endothelial cells are the most crucial cellular group within
arteries. Endothelial cells maintain the structure of the vessel
wall and keep it functional. In addition to acting as a barrier
between blood and subendothelial tissues, endothelial cells
have many different functions. These include creating a smooth
surface that prevents blood cells from adhering to the vascular
surface, secreting substances that promote and inhibit clotting
when needed, regulating the exchange of substances and fluids
between blood and tissues, sending paracrine signals that cause
contraction and relaxation of neighbouring smooth muscle cells,
secreting cytokines involved in the immune response, secreting
growth factors in response to damage, regulating angiogenesis
and vascular remodelling, removing hormones and some other
mediators [5, 6].
Even though the endothelium has so many important tasks to
perform, a disorder that can occur in its structure and function
can lead to life-threatening problems. Examples of these are
atherosclerosis and thrombosis. These types of diseases tend
to occur with age. This is because the accumulation of harmful
substances in the body increases with age, and the reduced ability
of cells to regenerate makes this situation easier [7, 8].
The common carotid artery, which was used in this study, is one
of the arteries with atherosclerosis and thrombosis. Atherosclerosis
and thrombosis in the common carotid artery can lead to life-
threatening conditions. As mentioned above, the common carotid
artery supplies blood to the head, particularly the brain. As a result
of narrowing and occlusion in these vessels, conditions such as
stroke, death, and cerebral palsy may occur [9]. For this reason,
the common carotid artery was chosen in this study. Although
previous studies have examined the changes in the vessels with
age, differences related to gender have not been elucidated. the
changes were examined that occur in the vessels with age differ
depending on gender.
MATERIALS AND METHODS
Animals
The experimental studies were performed in accordance with
the Declaration of Helsinki, Başkent University Research Center
Rules and Başkent University Experimental/Clinical Research
Principles. Sprague-Dawley rats (Norvegicus scutellaria) were obtained
from Başkent University Experimental Animal Production and
Research Center. The rats (Norvegicus scutellaria) were brought to
Başkent University Experimental Animal Production and Research
Center. Research Unit 10 days (d) before the diet administration to
acclimatize them to the environment, where they were divided into
old and young groups and housed with 2-3 animals in each cage in
an environment with constant temperature (25 ± 2°С) and relative
humidity (32 ± 7%), ventilated by a fan and with a 12-h light/dark
cycle. During this period, rats were fed standard chow (22% raw
protein, 9% raw ash, 7% raw cellulose, 3% raw fat BİL-YEM Food
Sanayi Ankara) and water was not restricted (ad libitum).
Study Groups
A total of 28 Sprague-Dawley rats, 14 males and 14 females,
were planned to be used in the study. Of these 28 rats, 4 females
and 4 males were constituted the control group. The rats in the
control group were 10 weeks old, and the rats in the experimental
group, which was represent the aged group, was 19 weeks old.
Surgical Procedure
All animals in the study were anaesthetised with 60 mg·kg -1
ketamine hydrochloride and 10 mg·kg-1 xylazine hydrochloride and
then sacrificed by removal of the heart. The right and left common
carotid arteries were removed from the sacrificed animals.
Histological Analysis
The removed vessels were immediately placed in a 0.1 M
phosphate buffered container containing 2.5% glutaraldehyde
for 24 h. The following morning, the vessels were postfixed in 1%
osmium tetraoxide (OsO4) in 0.1 M phosphate buffer for 1 hour
and dehydrated in a graded series of alcohols (25-100%). After
passing through propylene oxide, the samples were embedded in
Araldyte CY 212, DDSA (2-dodecenylsuccinic anhydride), BDMA
(benzyldimethylmethylamine) and dibutylphthalate. Semi-thin
sections (1 μm) taken transversely from the vessels were stained
with toluidine blue and examined by light microscopy (Carl Zeiss,
Göttingen Germany). Ultrathin sections of the arteries were
stained with uranyl acetate and lead citrate and examined by
transmission electron microscopy (TEM) (LEO 906E, Oberkochen,
Germany). TEM was preferred because it has advantages over other
microscopes in imaging ultrastructural cell architecture. For each
animal, at least four TEM images were taken from four different
sections from the same block.
INTRODUCTION
Common carotid arteries are the main arteries supplying the
head region. The right common carotid artery originates from the
arcus aorta and the left side from the brachiocephalic artery [1,
2]. The aorta and its branches are called elastic arteries. Elastic
arteries are responsible for the pulsatile progression of blood
through the vessel. In other words, they enable the blood pumped
by the heart throughout systole to flow during diastole. Elastic
arteries consist of tunica intima, tunica media and tunica adventitia.
The tunica intima comprises endothelium, subendothelial layer,
and internal elastic membrane.
The subendothelial layer contains collagen and elastic fibres
synthesised by smooth muscle cells. The tunica media is the
thickest layer in the elastic arteries and contains abundant layers
of elastic fibres. While the elastic fibre layers in this layer are
few or absent at birth, they gradually increase in number with
advancing age. The tunica adventitia consists of a connective layer
which is considerably thinner than the tunica media. Although
collagen fibres are present in all layers, their ratio in the adventitia
is higher, thus helping to keep the expansion of the vessel wall
within physiological limits during systole [3, 4].
Endothelial cells are the most crucial cellular group within
arteries. Endothelial cells maintain the structure of the vessel
wall and keep it functional. In addition to acting as a barrier
between blood and subendothelial tissues, endothelial cells
have many different functions. These include creating a smooth
surface that prevents blood cells from adhering to the vascular
surface, secreting substances that promote and inhibit clotting
when needed, regulating the exchange of substances and fluids
between blood and tissues, sending paracrine signals that cause
contraction and relaxation of neighbouring smooth muscle cells,
secreting cytokines involved in the immune response, secreting
growth factors in response to damage, regulating angiogenesis
and vascular remodelling, removing hormones and some other
mediators [5, 6].
Even though the endothelium has so many important tasks to
perform, a disorder that can occur in its structure and function
can lead to life-threatening problems. Examples of these are
atherosclerosis and thrombosis. These types of diseases tend
to occur with age. This is because the accumulation of harmful
substances in the body increases with age, and the reduced ability
of cells to regenerate makes this situation easier [7, 8].
The common carotid artery, which was used in this study, is one
of the arteries with atherosclerosis and thrombosis. Atherosclerosis
and thrombosis in the common carotid artery can lead to life-
threatening conditions. As mentioned above, the common carotid
artery supplies blood to the head, particularly the brain. As a result
of narrowing and occlusion in these vessels, conditions such as
stroke, death, and cerebral palsy may occur [9]. For this reason,
the common carotid artery was chosen in this study. Although
previous studies have examined the changes in the vessels with
age, differences related to gender have not been elucidated. the
changes were examined that occur in the vessels with age differ
depending on gender.
MATERIALS AND METHODS
Animals
The experimental studies were performed in accordance with
the Declaration of Helsinki, Başkent University Research Center
Rules and Başkent University Experimental/Clinical Research
Principles. Sprague-Dawley rats (Norvegicus scutellaria) were obtained
from Başkent University Experimental Animal Production and
Research Center. The rats (Norvegicus scutellaria) were brought to
Başkent University Experimental Animal Production and Research
Center. Research Unit 10 days (d) before the diet administration to
acclimatize them to the environment, where they were divided into
old and young groups and housed with 2-3 animals in each cage in
an environment with constant temperature (25 ± 2°С) and relative
humidity (32 ± 7%), ventilated by a fan and with a 12-h light/dark
cycle. During this period, rats were fed standard chow (22% raw
protein, 9% raw ash, 7% raw cellulose, 3% raw fat BİL-YEM Food
Sanayi Ankara) and water was not restricted (ad libitum).
Study Groups
A total of 28 Sprague-Dawley rats, 14 males and 14 females,
were planned to be used in the study. Of these 28 rats, 4 females
and 4 males were constituted the control group. The rats in the
control group were 10 weeks old, and the rats in the experimental
group, which was represent the aged group, was 19 weeks old.
Surgical Procedure
All animals in the study were anaesthetised with 60 mg·kg -1
ketamine hydrochloride and 10 mg·kg-1 xylazine hydrochloride and
then sacrificed by removal of the heart. The right and left common
carotid arteries were removed from the sacrificed animals.
Histological Analysis
The removed vessels were immediately placed in a 0.1 M
phosphate buffered container containing 2.5% glutaraldehyde
for 24 h. The following morning, the vessels were postfixed in 1%
osmium tetraoxide (OsO4) in 0.1 M phosphate buffer for 1 hour
and dehydrated in a graded series of alcohols (25-100%). After
passing through propylene oxide, the samples were embedded in
Araldyte CY 212, DDSA (2-dodecenylsuccinic anhydride), BDMA
(benzyldimethylmethylamine) and dibutylphthalate. Semi-thin
sections (1 μm) taken transversely from the vessels were stained
with toluidine blue and examined by light microscopy (Carl Zeiss,
Göttingen Germany). Ultrathin sections of the arteries were
stained with uranyl acetate and lead citrate and examined by
transmission electron microscopy (TEM) (LEO 906E, Oberkochen,
Germany). TEM was preferred because it has advantages over other
microscopes in imaging ultrastructural cell architecture. For each
animal, at least four TEM images were taken from four different
sections from the same block.
_________________________________________________________________________________________________Scientific Journal, FCV-LUZ / Vol.XXXV3 of 8
RESULTS AND DISCUSSION
As expected in young rats in control group, the endothelial cells
continue with subendothelial layer and internal elastic lamina. The
nucleus of the endothelial cell appears homogeneously distributed
with euchromatin-rich cytoplasm. The basal lamina was continuous
with the endothelial cell and retains its normal structure. In the
control male, natural looking elastic fibres were also seen in the
medium tunic (FIG. 1).
The endothelial cells in the provided observations demonstrate
a series of notable changes in old female (OF) rats (FIG. 2)
Initially, these cells exhibit separation from the basal lamina
in certain areas (FIG. 2 OF–1), while in other instances, they
revealed polyploid nuclei and enlargement (FIG. 2 OF–2). This
change is accompanied by an increase in heterochromatin and
a karyorrhectic appearance in the endothelial cell nuclei (FIG. 2
OF–3), indicating a subsequent shrinkage and degeneration within
the nucleus, along with apoptotic characteristics visible in the
cell’s appearance. Furthermore, a darkening of the cell nuclei is
evident (FIG. 2 OF–4). Furthermore, alterations manifest in the
subendothelial layer, irregular smooth muscle (SC) cell growth,
and excessive disruption of the endothelium (FIG. 2 OF–5).
As a result, collagen accumulates due to the compromised
integrity of the internal elastic lamina (IEL) extending from the
basal lamina (FIG. 2 OF–6). Other notable changes include the
cell nucleus degenerating in favour of apoptosis, leading to the
formation of bubbles in the plasma membrane and vacuole–
like spaces in the cytoplasm. Accumulations of collagen–like
material are witnessed under the IEL (FIG. 2 OF–7). The cells
exhibit cytoplasmic protrusions towards the lumen, alongside
disrupted cell boundaries and the accumulation of vesicles in
the cytoplasm (FIG. 2 OF–8). Additionally, the endothelial cells
display vacuolation in multiple areas, and a separation is noted
between the IEL and the underlying tissue (FIG. 2 OF–9), ultimately
resulting in a corrugated appearance of the basal lamina. These
observations collectively depict a series of significant and varied
alterations occurring within the endothelial cells.
The histological examination revealed multiple various features
across the endothelial layers. The endothelial cells in the provided
observations demonstrate a series of notable changes in old male
(OM) rats, as illustrated in FIG. 3. Large gaps were evident in the
endothelium with separation from the basal lamina, accompanied
by a dense accumulation of collagen under the IEL (FIG. 3 OM–1).
Nuclear changes, such as increased heterochromatin distribution
and cytoplasmic vacuolization, were observed alongside
intracellular lipid–like structures (FIG. 3 OM–2). Moreover,
abnormalities included the formation of large vacuoles in the
endothelial cells, irregular folds in the basal lamina surrounding
the nucleus, and disruptions in the IEL (FIG. 3 OM–3, OM–4). These
changes were accompanied by polyploid nuclei, matrix disturbances
in the tunica media, and signs of inflammation, suggested by
leukocyte diapedesis and platelet presence, potentially indicating
a background of endothelial cell necroptosis (FIG. 3 OM–5, OM–6).
Additionally, endothelial degeneration, infiltration of lymphocytes,
and the presence of vacuoles with possible lipid precursors were
noted (FIG. 3 OM–7). The discontinuity of the endothelial line and
basal lamina, along with detached endothelial cells, illustrated
structural disarray (FIG. 3 OM–8, OM–9). Furthermore, pyknotic
changes in the nucleus, smooth muscle cell irregularities in the
tunica media, and subendothelial collagen accumulations due to
detachment of the endothelial cells were observed throughout the
tissue (FIG. 3 OM–10).
In a study of bovine aortic and microvascular endothelial
cells, overgrowth and enlargement of cells were observed in the
bovine aortic endothelium with increasing age. It was suggested
that this was due to reduced cell renewal or filling of the gap in
the endothelium by migrating cells rather than dying cells [10].
In a study on the effect of aging on vasoactivity in monkeys,
although thickening of the tunica intima was observed with
aging, atherosclerosis did not develop. It has been suggested
that apoptosis in endothelial cells may cause loss of endothelial
function due to decreased cell density [11]. Another study in
mice showed that intense endothelial apoptosis occurs in the
FIGURE 1. Control group electromicrographs (control female on the left X7750, control male on the right X6000) (Sub: Subendothelial layer, IEL:
Internal Elastic Lamina, E: Endothelial Cell, N: Nucleus of the Endothelial cell, EF: Elastic Fibres, →: Basal Lamina)
RESULTS AND DISCUSSION
As expected in young rats in control group, the endothelial cells
continue with subendothelial layer and internal elastic lamina. The
nucleus of the endothelial cell appears homogeneously distributed
with euchromatin-rich cytoplasm. The basal lamina was continuous
with the endothelial cell and retains its normal structure. In the
control male, natural looking elastic fibres were also seen in the
medium tunic (FIG. 1).
The endothelial cells in the provided observations demonstrate
a series of notable changes in old female (OF) rats (FIG. 2)
Initially, these cells exhibit separation from the basal lamina
in certain areas (FIG. 2 OF–1), while in other instances, they
revealed polyploid nuclei and enlargement (FIG. 2 OF–2). This
change is accompanied by an increase in heterochromatin and
a karyorrhectic appearance in the endothelial cell nuclei (FIG. 2
OF–3), indicating a subsequent shrinkage and degeneration within
the nucleus, along with apoptotic characteristics visible in the
cell’s appearance. Furthermore, a darkening of the cell nuclei is
evident (FIG. 2 OF–4). Furthermore, alterations manifest in the
subendothelial layer, irregular smooth muscle (SC) cell growth,
and excessive disruption of the endothelium (FIG. 2 OF–5).
As a result, collagen accumulates due to the compromised
integrity of the internal elastic lamina (IEL) extending from the
basal lamina (FIG. 2 OF–6). Other notable changes include the
cell nucleus degenerating in favour of apoptosis, leading to the
formation of bubbles in the plasma membrane and vacuole–
like spaces in the cytoplasm. Accumulations of collagen–like
material are witnessed under the IEL (FIG. 2 OF–7). The cells
exhibit cytoplasmic protrusions towards the lumen, alongside
disrupted cell boundaries and the accumulation of vesicles in
the cytoplasm (FIG. 2 OF–8). Additionally, the endothelial cells
display vacuolation in multiple areas, and a separation is noted
between the IEL and the underlying tissue (FIG. 2 OF–9), ultimately
resulting in a corrugated appearance of the basal lamina. These
observations collectively depict a series of significant and varied
alterations occurring within the endothelial cells.
The histological examination revealed multiple various features
across the endothelial layers. The endothelial cells in the provided
observations demonstrate a series of notable changes in old male
(OM) rats, as illustrated in FIG. 3. Large gaps were evident in the
endothelium with separation from the basal lamina, accompanied
by a dense accumulation of collagen under the IEL (FIG. 3 OM–1).
Nuclear changes, such as increased heterochromatin distribution
and cytoplasmic vacuolization, were observed alongside
intracellular lipid–like structures (FIG. 3 OM–2). Moreover,
abnormalities included the formation of large vacuoles in the
endothelial cells, irregular folds in the basal lamina surrounding
the nucleus, and disruptions in the IEL (FIG. 3 OM–3, OM–4). These
changes were accompanied by polyploid nuclei, matrix disturbances
in the tunica media, and signs of inflammation, suggested by
leukocyte diapedesis and platelet presence, potentially indicating
a background of endothelial cell necroptosis (FIG. 3 OM–5, OM–6).
Additionally, endothelial degeneration, infiltration of lymphocytes,
and the presence of vacuoles with possible lipid precursors were
noted (FIG. 3 OM–7). The discontinuity of the endothelial line and
basal lamina, along with detached endothelial cells, illustrated
structural disarray (FIG. 3 OM–8, OM–9). Furthermore, pyknotic
changes in the nucleus, smooth muscle cell irregularities in the
tunica media, and subendothelial collagen accumulations due to
detachment of the endothelial cells were observed throughout the
tissue (FIG. 3 OM–10).
In a study of bovine aortic and microvascular endothelial
cells, overgrowth and enlargement of cells were observed in the
bovine aortic endothelium with increasing age. It was suggested
that this was due to reduced cell renewal or filling of the gap in
the endothelium by migrating cells rather than dying cells [10].
In a study on the effect of aging on vasoactivity in monkeys,
although thickening of the tunica intima was observed with
aging, atherosclerosis did not develop. It has been suggested
that apoptosis in endothelial cells may cause loss of endothelial
function due to decreased cell density [11]. Another study in
mice showed that intense endothelial apoptosis occurs in the
FIGURE 1. Control group electromicrographs (control female on the left X7750, control male on the right X6000) (Sub: Subendothelial layer, IEL:
Internal Elastic Lamina, E: Endothelial Cell, N: Nucleus of the Endothelial cell, EF: Elastic Fibres, →: Basal Lamina)
Ultrastructural changes in the common carotid artery in Rat model / Ünlükal _______________________________________________________4 of 8
FIGURE 2. Electromicrographs of the old female group.F–1,2,6,8 6000×; OF–3 12930×; OF–4 4446×, OF–5 3597×; OF–7 10000×; OF–9 7750×. In OF–1,2,5,6,
endothelial (E) cells are separated from the basal lamina (indicated by arrowhead) and desquamated in places. In OF–5,6,7, endothelial cells have polyploid
nuclei and enlarged. OF–1. Heterochromatin increase and karyorrhectic appearance were observed in endothelial cell nuclei. OF–2. Shrinkage and
degeneration started in the cell nucleus. The cell exhibits apoptotic appearance with bubbles in the plasma membrane. OF–3. Darkening was observed in
the cell nucleus and increased vacuolisation was observed around the plasma membrane close to the basal lamina. OF–4. Thickening of the subendothelial
layer and irregular growth of smooth muscle (SC) cells and excessive disruption of the endothelium were observed. OF–5. Collagen accumulated as a
result of disruption of the integrity of the IEL protruded from the basal lamina. OF–6. Cell nucleus degenerated by strangulation in favour of apoptosis,
bubbles are formed in the plasma membrane, vacuole–like spaces are seen in the cytoplasm. Accumulations of collagen–like material are seen under
the IEL. OF–7. Cytoplasmic protrusion is seen towards the lumen with disrupted cell boundaries. Accumulations of vesicles are seen in the cytoplasm.
OF–8. Endothelial cell is vacuolated in more than one place. Separation was seen between the IEL and the underlying tissue. OF–9. The basal lamina has
a corrugated appearance. (E: endothelial cell, N: nucleus, IEL: internal elastic lamina, SC: smooth muscle cell, v: vacuole, Coll: collagen, →: basal lamina)
FIGURE 2. Electromicrographs of the old female group.F–1,2,6,8 6000×; OF–3 12930×; OF–4 4446×, OF–5 3597×; OF–7 10000×; OF–9 7750×. In OF–1,2,5,6,
endothelial (E) cells are separated from the basal lamina (indicated by arrowhead) and desquamated in places. In OF–5,6,7, endothelial cells have polyploid
nuclei and enlarged. OF–1. Heterochromatin increase and karyorrhectic appearance were observed in endothelial cell nuclei. OF–2. Shrinkage and
degeneration started in the cell nucleus. The cell exhibits apoptotic appearance with bubbles in the plasma membrane. OF–3. Darkening was observed in
the cell nucleus and increased vacuolisation was observed around the plasma membrane close to the basal lamina. OF–4. Thickening of the subendothelial
layer and irregular growth of smooth muscle (SC) cells and excessive disruption of the endothelium were observed. OF–5. Collagen accumulated as a
result of disruption of the integrity of the IEL protruded from the basal lamina. OF–6. Cell nucleus degenerated by strangulation in favour of apoptosis,
bubbles are formed in the plasma membrane, vacuole–like spaces are seen in the cytoplasm. Accumulations of collagen–like material are seen under
the IEL. OF–7. Cytoplasmic protrusion is seen towards the lumen with disrupted cell boundaries. Accumulations of vesicles are seen in the cytoplasm.
OF–8. Endothelial cell is vacuolated in more than one place. Separation was seen between the IEL and the underlying tissue. OF–9. The basal lamina has
a corrugated appearance. (E: endothelial cell, N: nucleus, IEL: internal elastic lamina, SC: smooth muscle cell, v: vacuole, Coll: collagen, →: basal lamina)
_________________________________________________________________________________________________Scientific Journal, FCV-LUZ / Vol.XXXV5 of 8
FIGURE 3. Electromicrographs of the old male group OM–1 10000×; OM–2.4 12930×; OM–3.6 4646×; OM–5 3597×; OM–7 16700×; OM–8 1670×; OM–9.10 2784×. Detailed
description of the ultrastructural structures of the cells depicted in the figure above. OM-1. Large gaps formation in the endothelium and separation from the basal
lamina were observed. There is dense collagen accumulation under the IEL. OM-2. Heterochromatin distribution was observed to increase with increasing nuclear
indentation and large cytoplasmic vacuoles were formed. Intracellular accumulations thought to be of lipid structure are seen. OM-3. There is large vacuole formation
in the endothelial cell. Collagen accumulation is seen under the IEL. Heterogenic structure is seen in the upper right cytoplasm. OM-4: The nucleus is abnormally
surrounded by vacuoles and irregular folds are formed in the basal lamina. OM-5. Endothelial polyploid nucleus and desquamation, disruption in the IEL, disruptions
and accumulations in the subendothelial layer, structural disturbances in the matrix in the tunica media are present. The presence of platelets and leukocyte diapedesis
were evaluated in favour of inflammation. Apoptotic changes in the endothelium against a background of inflammation suggested necroptosis. OM-6. The endothelial
cell has a degenerated appearance with polyploid nuclei and is separated from the basal lamina. The subendothelial layer has a large number of folds and cavities.
There was also accumulations in the subendothelial layer. Infiltrated lymphocytes are seen adjacent to the endothelial cells. OM-7. Single vacuole is seen in the
cytoplasm with a grey oil droplet. The grey lipid droplet may be a precursor of lipofuscin. Collagen deposition and fluctuations in the basal lamina are seen under the
IEL. OM-8. The endothelial line is separated from the basal lamina and does not show continuity. OM-9. Discontinuity in the basal lamina and subendothelial collagen
accumulation due to detachment of the endothelial cell. OM-10. The nucleus exhibits a pyknotic appearance. There are places where the endothelial cell is detached
from the basal lamina. In the tunica media there is an irregular smooth muscle cell which has lost its spindle shape. (E: endothelial cell, N: nucleus, IEL: internal elastic
lamina, DC: smooth muscle cell, v: vacuole, Col: collagen, Leu: leukocyte, T: platelet, L: lymphocyte, →: basal lamina)
FIGURE 3. Electromicrographs of the old male group OM–1 10000×; OM–2.4 12930×; OM–3.6 4646×; OM–5 3597×; OM–7 16700×; OM–8 1670×; OM–9.10 2784×. Detailed
description of the ultrastructural structures of the cells depicted in the figure above. OM-1. Large gaps formation in the endothelium and separation from the basal
lamina were observed. There is dense collagen accumulation under the IEL. OM-2. Heterochromatin distribution was observed to increase with increasing nuclear
indentation and large cytoplasmic vacuoles were formed. Intracellular accumulations thought to be of lipid structure are seen. OM-3. There is large vacuole formation
in the endothelial cell. Collagen accumulation is seen under the IEL. Heterogenic structure is seen in the upper right cytoplasm. OM-4: The nucleus is abnormally
surrounded by vacuoles and irregular folds are formed in the basal lamina. OM-5. Endothelial polyploid nucleus and desquamation, disruption in the IEL, disruptions
and accumulations in the subendothelial layer, structural disturbances in the matrix in the tunica media are present. The presence of platelets and leukocyte diapedesis
were evaluated in favour of inflammation. Apoptotic changes in the endothelium against a background of inflammation suggested necroptosis. OM-6. The endothelial
cell has a degenerated appearance with polyploid nuclei and is separated from the basal lamina. The subendothelial layer has a large number of folds and cavities.
There was also accumulations in the subendothelial layer. Infiltrated lymphocytes are seen adjacent to the endothelial cells. OM-7. Single vacuole is seen in the
cytoplasm with a grey oil droplet. The grey lipid droplet may be a precursor of lipofuscin. Collagen deposition and fluctuations in the basal lamina are seen under the
IEL. OM-8. The endothelial line is separated from the basal lamina and does not show continuity. OM-9. Discontinuity in the basal lamina and subendothelial collagen
accumulation due to detachment of the endothelial cell. OM-10. The nucleus exhibits a pyknotic appearance. There are places where the endothelial cell is detached
from the basal lamina. In the tunica media there is an irregular smooth muscle cell which has lost its spindle shape. (E: endothelial cell, N: nucleus, IEL: internal elastic
lamina, DC: smooth muscle cell, v: vacuole, Col: collagen, Leu: leukocyte, T: platelet, L: lymphocyte, →: basal lamina)
Ultrastructural changes in the common carotid artery in Rat model / Ünlükal _______________________________________________________6 of 8
capillaries that supply muscle with age [12]. In the study showing
that increased fluid shear stress mediates recovery in aged
endothelium, it was stated that ageing leads to an increase in
polyploid nuclei, irregular cell shape and size growth in endothelial
cells. Furthermore, subendothelial matrix thickening, lipofuscin-
like structures and apoptotic endothelial cells were observed [13].
In a study investigating the effect of ageing on the common iliac
artery in rats, it was found that in old rats, gaps were observed
between endothelial cells, collagen increased, elastic fibres
decreased, endothelial cells and smooth muscle cells died, and
a picture characterised by chromatin degradation and cell lysis was
observed [14]. Similarly, endothelial cells with polyploid nuclei,
irregular shape and apopitotic endothelial cells were observed in
our study. Endothelial cell desquamation explains the decrease
in cell density.
A study of the carotid body in the common carotid artery
reported that atherosclerosis did not occur despite thickening of
the vessel wall and rupture of elastic bands with age [15]. In this
study, a deterioration in the integrity of the IEL was also observed.
Studies on angiotensin II (Ang II) in rats have reported that Ang II
increases the activity of matrix metalloproteinases (MMPs) and
increases the collagen ratio in the tunica intima and tunica
media. In the same study, morphological changes in the vessels
similar to those in old rats were observed as a result of Ang II
infusion in young rats [16]. A similar study in rats reported that
age-related physiopathological changes such as proinflammation,
vasoconstriction, elastin degeneration, collagen accumulation
are related to MMPs and lead to atherosclerosis and increased
blood pressure [17]. In light of these studies, we thought that the
deterioration of IEL integrity, collagen accumulation in the tunica
media and tunica intima, and decrease in the amount of elastin
in the tunica media observed in our study may be age-related
increased MMP activation. In addition, MMP activation stimulates
thrombosis of matrix fragments, which may induce inflammation.
In a study investigating the age-related changes in the aortic
intima caused by diet-induced hypercholesterolemia in rats,
increased lipid droplets and Golgi complexes were observed in
24-month-old fat-fed rats, whereas huge electron dense clusters
concentrated around the IEL were observed in 24-month-old
control rats. In 24-month-old control rats, endothelial cell junctions
were indistinct and irregular in appearance. Cytoplasmic areas
were found on the endothelial cell membrane that protrude into
the lumen in the study. Slightly increased monocyte adhesion
is observed in the endothelium of 24-month-old control rats
compared with 24-month-old fat-fed rats [18]. Intercellular
disruption, accumulation in the subendothelial layer and monocyte
adhesion were also present in this study. This study suggests
that age-related deterioration of the vascular wall may occur
independently of diet.
Increased tumour necrosis factor-alpha (TNF-a), caspase-9
regulation and decreased NO bioavailability with age stimulate
apoptosis in endothelial cells. This may lead to impaired
endothelial function and ischaemia in the elderly [19]. Decreased
mitochondrial function with age leads to an increase in reactive
oxygen species (ROS) and triggers vascular inflammation [20].
One study reports that the number of monocytes infiltrating the
intima increases with age. The reason for the increase in monocyte
infiltration has been explained by the increased expression of
intercellular adhesion molecule-1 (ICAM-1) and vascular cell
adhesion molecule-1 (VCAM-1) on endothelial cells with age
[21]. Ageing endothelial cells become more widespread, enlarged
and have increasingly polyploid nuclei. These are all effects of
cellular senescence. The ageing of endothelial cells leads to a
loss of function, a proinflammatory and proapoptotic state, which
increases monocyte migration [22]. In comparison with the above
information, it can be conclude that similar changes occurred in our
study. Decreased number of mitochondria and structural disruption
of mitochondria trigger both apoptosis and inflammation.
In an article comparing age-related endothelial dysfunction in
women and men, it was explained that women are affected 10 years
later than men. The reason for this is not the effect of estrogen on
the plasma lipid ratio, but its proliferative effect on the cell. The
decreasing amount of estrogen after menopause brings the level
of postmenopausal endothelial dysfunction to the same level as in
men [23]. A human study investigated the effect of ageing on the
aortic wall. In the study, a thickening of the vessel wall with age was
observed. In the vascular matrix, elastin decreases with age, while
the amount of collagen increases. Depending on gender, collagen
predominates in the matrix in women, whereas elastin and smooth
muscle cells predominate in men [3].
In this study, it can be said that male rats have more collagen
accumulation in the subendothelial layer and leukocyte infiltration
in the tunica intima. These may be due to the anti-inflammatory
and proliferative effects of estrogen in the cardiovascular system
[24]. On the other hand, apoptotic endothelial cells, desquamation,
vacuolisation, defects in the basal lamina and disruption of IEL
integrity were observed at similar rates in both male and female rats.
In this study, intracellular vacuolisation was observed in both
male and female groups as single large vacuole or multiple small
vacuoles. A similar situation was not observed in previous studies.
It is speculated that this is due to autophagic vacuoles that increase
with age.
CONCLUSION
When it was examined the effects of ageing on the common
carotid artery ultrastructurally, similar to previous studies, it was
observed deviations from the conditions that should be present
in both the cellular dimension and the intercellular matrix, even
in the absence of atheroma and atherosclerosis formation.
Loss of elastin in the matrix, collagen accumulation and loss of
elasticity as a result of IEL damage explain arterial stiffness. We
know that inflammation in the tunica intima with aging triggers
matrix degradation and cellular damage. As seen in our study, we
can say that females are less affected by ageing at the vascular
level compared to males. Although we think this is due to the
anti-inflammatory and proliferative effects of estrogen, we have
no data on this. We think that the effects of estrogen should be
investigated ultrastructurally in future studies to better understand
the difference in vascular ageing between men and women.
Funding
No funding.
capillaries that supply muscle with age [12]. In the study showing
that increased fluid shear stress mediates recovery in aged
endothelium, it was stated that ageing leads to an increase in
polyploid nuclei, irregular cell shape and size growth in endothelial
cells. Furthermore, subendothelial matrix thickening, lipofuscin-
like structures and apoptotic endothelial cells were observed [13].
In a study investigating the effect of ageing on the common iliac
artery in rats, it was found that in old rats, gaps were observed
between endothelial cells, collagen increased, elastic fibres
decreased, endothelial cells and smooth muscle cells died, and
a picture characterised by chromatin degradation and cell lysis was
observed [14]. Similarly, endothelial cells with polyploid nuclei,
irregular shape and apopitotic endothelial cells were observed in
our study. Endothelial cell desquamation explains the decrease
in cell density.
A study of the carotid body in the common carotid artery
reported that atherosclerosis did not occur despite thickening of
the vessel wall and rupture of elastic bands with age [15]. In this
study, a deterioration in the integrity of the IEL was also observed.
Studies on angiotensin II (Ang II) in rats have reported that Ang II
increases the activity of matrix metalloproteinases (MMPs) and
increases the collagen ratio in the tunica intima and tunica
media. In the same study, morphological changes in the vessels
similar to those in old rats were observed as a result of Ang II
infusion in young rats [16]. A similar study in rats reported that
age-related physiopathological changes such as proinflammation,
vasoconstriction, elastin degeneration, collagen accumulation
are related to MMPs and lead to atherosclerosis and increased
blood pressure [17]. In light of these studies, we thought that the
deterioration of IEL integrity, collagen accumulation in the tunica
media and tunica intima, and decrease in the amount of elastin
in the tunica media observed in our study may be age-related
increased MMP activation. In addition, MMP activation stimulates
thrombosis of matrix fragments, which may induce inflammation.
In a study investigating the age-related changes in the aortic
intima caused by diet-induced hypercholesterolemia in rats,
increased lipid droplets and Golgi complexes were observed in
24-month-old fat-fed rats, whereas huge electron dense clusters
concentrated around the IEL were observed in 24-month-old
control rats. In 24-month-old control rats, endothelial cell junctions
were indistinct and irregular in appearance. Cytoplasmic areas
were found on the endothelial cell membrane that protrude into
the lumen in the study. Slightly increased monocyte adhesion
is observed in the endothelium of 24-month-old control rats
compared with 24-month-old fat-fed rats [18]. Intercellular
disruption, accumulation in the subendothelial layer and monocyte
adhesion were also present in this study. This study suggests
that age-related deterioration of the vascular wall may occur
independently of diet.
Increased tumour necrosis factor-alpha (TNF-a), caspase-9
regulation and decreased NO bioavailability with age stimulate
apoptosis in endothelial cells. This may lead to impaired
endothelial function and ischaemia in the elderly [19]. Decreased
mitochondrial function with age leads to an increase in reactive
oxygen species (ROS) and triggers vascular inflammation [20].
One study reports that the number of monocytes infiltrating the
intima increases with age. The reason for the increase in monocyte
infiltration has been explained by the increased expression of
intercellular adhesion molecule-1 (ICAM-1) and vascular cell
adhesion molecule-1 (VCAM-1) on endothelial cells with age
[21]. Ageing endothelial cells become more widespread, enlarged
and have increasingly polyploid nuclei. These are all effects of
cellular senescence. The ageing of endothelial cells leads to a
loss of function, a proinflammatory and proapoptotic state, which
increases monocyte migration [22]. In comparison with the above
information, it can be conclude that similar changes occurred in our
study. Decreased number of mitochondria and structural disruption
of mitochondria trigger both apoptosis and inflammation.
In an article comparing age-related endothelial dysfunction in
women and men, it was explained that women are affected 10 years
later than men. The reason for this is not the effect of estrogen on
the plasma lipid ratio, but its proliferative effect on the cell. The
decreasing amount of estrogen after menopause brings the level
of postmenopausal endothelial dysfunction to the same level as in
men [23]. A human study investigated the effect of ageing on the
aortic wall. In the study, a thickening of the vessel wall with age was
observed. In the vascular matrix, elastin decreases with age, while
the amount of collagen increases. Depending on gender, collagen
predominates in the matrix in women, whereas elastin and smooth
muscle cells predominate in men [3].
In this study, it can be said that male rats have more collagen
accumulation in the subendothelial layer and leukocyte infiltration
in the tunica intima. These may be due to the anti-inflammatory
and proliferative effects of estrogen in the cardiovascular system
[24]. On the other hand, apoptotic endothelial cells, desquamation,
vacuolisation, defects in the basal lamina and disruption of IEL
integrity were observed at similar rates in both male and female rats.
In this study, intracellular vacuolisation was observed in both
male and female groups as single large vacuole or multiple small
vacuoles. A similar situation was not observed in previous studies.
It is speculated that this is due to autophagic vacuoles that increase
with age.
CONCLUSION
When it was examined the effects of ageing on the common
carotid artery ultrastructurally, similar to previous studies, it was
observed deviations from the conditions that should be present
in both the cellular dimension and the intercellular matrix, even
in the absence of atheroma and atherosclerosis formation.
Loss of elastin in the matrix, collagen accumulation and loss of
elasticity as a result of IEL damage explain arterial stiffness. We
know that inflammation in the tunica intima with aging triggers
matrix degradation and cellular damage. As seen in our study, we
can say that females are less affected by ageing at the vascular
level compared to males. Although we think this is due to the
anti-inflammatory and proliferative effects of estrogen, we have
no data on this. We think that the effects of estrogen should be
investigated ultrastructurally in future studies to better understand
the difference in vascular ageing between men and women.
Funding
No funding.
_________________________________________________________________________________________________Scientific Journal, FCV-LUZ / Vol.XXXV7 of 8
Author Information
Department of Histology and Embryology, Faculty of Medicine,
Konya, Turkey
Ethical approval
The study was approved by the Ethical Committee of the Faculty
of Medicine of Baskent University. The ethics approval number
is 2009/16.
Consent for publication
The author has participated in the design, execution, and analysis
of the paper and has approved the final version.
Conflict of interest
No author has a financial or proprietary interest in any part of
the study.
BIBLIOGRAPHIC REFERENCES
[1] Humphrey JD, McCulloch AD. The cardiovascular system -
Anatomy, physiology and cell biology. In: Holzapfel GA, Ogden
RW, editors. Biomechanics of soft tissue in cardiovascular
systems [Internet]. Vienna (Austria): Springer; 2003. p. 1-14.
doi: https://doi.org/n5bm
[2] Laizzo PA. Handbook of cardiac anatomy, physiology, and
devices. 2nd ed. [Internet]. Totowa (NJ, USA): Humana Press;
2009. 700 pp. doi: https://doi.org/dt88sf
[3] Albu M, Şeicaru DA, Pleşea RM, Mirea OC, Gherghiceanu F,
Grigorean VT, Cordoş L, Liţescu M, Pleşea LE, Serbanescu
MS. Assessment of the aortic wall histological changes with
ageing. Rom. J. Morp. Embryol. [Internet]. 2021; 62(1):85-
100. doi: https://doi.org/g832mh
[4] Pawlina W. Histology: A text and atlas: with correlated cell
and molecular biology. 9th ed. Philadelphia (PA, USA): Wolters
Kluwer Health; 2023. 1104 p.
[5] Hall JE. Guyton and Hall Textbook of medical physiology. 12th
ed. Philadelphia (PA, USA): Saunders; 2011. 1091 p.
[6] Krüger-Genge A, Blocki A, Franke RP, Jung F. Vascular
endothelial cell biology: An update. Int. J. Mol. Sci. [Internet].
2019; 20(18):4411. doi: https://doi.org/ghvvj6
[7] Kaur J, Farr JN. Cellular senescence in age-related disorders.
Transl. Res. [Internet]. 2020; 226:96-104. doi: https://doi.
org/gmgncx
[8] Owens WA, Walaszczyk A, Spyridopoulos I, Dookun E,
Richardson GD. Senescence and senolytics in cardiovascular
disease: Promise and potential pitfalls. Mech. Ageing Dev.
[Internet]. 2021; 198:111540. doi: https://doi.org/gspvxx
[9] Murphy SJ, Werring DJ. Stroke: causes and clinical features.
Medicine [Internet]. 2020; 48(9):561-566. doi: https://doi.
org/gpzh7c
[10] Cavallaro U, Castelli V, Del Monte U, Soria MR. Phenotypic
alterations in senescent large-vessel and microvascular
endothelial cells. Mol. Cell. Biol. Res. Commun. [Internet].
2000; 4(2):117-121. doi: https://doi.org/fvgmc8
[11] Asai K, Kudej RK, Shen YT, Yang GP, Takagi G, Kudej AB, Geng
YJ, Sato N, Nazareno JB, Vatner DE, Natividad F, Bishop SP,
Vatner SF. Peripheral vascular endothelial dysfunction and
apoptosis in old monkeys. Arterioscler. Thromb. Vasc. Biol.
[Internet]. 2000; 20(6):1493-1499. doi: https://doi.org/fv6m7b
[12] Wang H, Listrat A, Meunier B, Gueugneau M, Coudy-Gandilhon.
C, Combaret L, Taillandier D, Polge C, Attaix D, Lethias C,
Lee K, Goh KL, Béchet D. Apoptosis in capillary endothelial
cells in ageing skeletal muscle. Aging Cell. [Internet]. 2014;
13(2):254-262. doi: https://doi.org/gcbqs9
[13] Dong L, Gan L, Wang H, Cai W. Age-Related impairment of
structure and function of iliac artery endothelium in rats is
improved by elevated fluid shear stress. Med. Sci. Monit.
[Internet]. 2019; 25:5127-5136. doi: https://doi.org/g832mj
[14] Liping D, Jia L, Guangyi L, Heng Y. [Effect of aging on the
ultrastructure of common iliac artery in rats]. Chinese J. Tiss.
Eng. Res. [Internet]. 2022; 26(26):4123-4126. Chinese. doi:
https://doi.org/g832mk
[15] Dymecka A, Walski M, Pokorski M. Ultrastructural degradation of
the carotid body in the aged rat: Is there a role for atherosclerosis
in the main carotid arteries? J. Physiol. Pharmacol. [Internet].
2006 [cited 24 Jun. 2024]; 57(Suppl.4):85-90. PMID: 17072033.
Available in: https://goo.su/VoAEp
[16] Wang M, Zhang J, Spinetti G, Jiang LQ, Monticone R, Zhao
D, Cheng L, Krawczyk M, Talan M, Pintus G, Lakatta EG.
Angiotensin II activates matrix metalloproteinase type II
and mimics age-associated carotid arterial remodeling in
young rats. Am. J. Pathol. [Internet]. 2005; 167(5):1429-
1442. doi: https://doi.org/cs2xbf
[17] Wang M, Zhang J, Telljohann R, Jiang L, Wu J, Monticone
RE, Kapoor K, Talan M, Lakatta EG. Chronic matrix
metalloproteinase inhibition retards age-associated arterial
proinflammation and increase in blood pressure. Hypertension
[Internet]. 2012; 60(2):459-466. doi: https://doi.org/f4s22p
[18] Nakamura H, Izumiyama N, Nakamura K, Ohtsubo K.
Age-associated ultrastructural changes in the aortic intima of
rats with diet-induced hypercholesterolemia. Atherosclerosis
[Internet]. 1989; 79(2):101-111. doi: https://doi.org/fv89tn
[19] Csiszar A, Ungvari Z, Koller A, Edwards JG, Kaley G.
Proinflammatory phenotype of coronary arteries promotes
endothelial apoptosis in aging. Physiol. Genomics [Internet].
2004; 17(1):21-30. doi: https://doi.org/d5bsdw
[20] Ungvari Z, Labinskyy N, Gupte S, Chander PN, Edwards
JG, Csiszar A. Dysregulation of mitochondrial biogenesis
in vascular endothelial and smooth muscle cells of aged
rats. Am. J. Physio. Heart Circ. Physiol. [Internet]. 2008;
294(5):H2121-H2128. doi: https://doi.org/bntnzc
Author Information
Department of Histology and Embryology, Faculty of Medicine,
Konya, Turkey
Ethical approval
The study was approved by the Ethical Committee of the Faculty
of Medicine of Baskent University. The ethics approval number
is 2009/16.
Consent for publication
The author has participated in the design, execution, and analysis
of the paper and has approved the final version.
Conflict of interest
No author has a financial or proprietary interest in any part of
the study.
BIBLIOGRAPHIC REFERENCES
[1] Humphrey JD, McCulloch AD. The cardiovascular system -
Anatomy, physiology and cell biology. In: Holzapfel GA, Ogden
RW, editors. Biomechanics of soft tissue in cardiovascular
systems [Internet]. Vienna (Austria): Springer; 2003. p. 1-14.
doi: https://doi.org/n5bm
[2] Laizzo PA. Handbook of cardiac anatomy, physiology, and
devices. 2nd ed. [Internet]. Totowa (NJ, USA): Humana Press;
2009. 700 pp. doi: https://doi.org/dt88sf
[3] Albu M, Şeicaru DA, Pleşea RM, Mirea OC, Gherghiceanu F,
Grigorean VT, Cordoş L, Liţescu M, Pleşea LE, Serbanescu
MS. Assessment of the aortic wall histological changes with
ageing. Rom. J. Morp. Embryol. [Internet]. 2021; 62(1):85-
100. doi: https://doi.org/g832mh
[4] Pawlina W. Histology: A text and atlas: with correlated cell
and molecular biology. 9th ed. Philadelphia (PA, USA): Wolters
Kluwer Health; 2023. 1104 p.
[5] Hall JE. Guyton and Hall Textbook of medical physiology. 12th
ed. Philadelphia (PA, USA): Saunders; 2011. 1091 p.
[6] Krüger-Genge A, Blocki A, Franke RP, Jung F. Vascular
endothelial cell biology: An update. Int. J. Mol. Sci. [Internet].
2019; 20(18):4411. doi: https://doi.org/ghvvj6
[7] Kaur J, Farr JN. Cellular senescence in age-related disorders.
Transl. Res. [Internet]. 2020; 226:96-104. doi: https://doi.
org/gmgncx
[8] Owens WA, Walaszczyk A, Spyridopoulos I, Dookun E,
Richardson GD. Senescence and senolytics in cardiovascular
disease: Promise and potential pitfalls. Mech. Ageing Dev.
[Internet]. 2021; 198:111540. doi: https://doi.org/gspvxx
[9] Murphy SJ, Werring DJ. Stroke: causes and clinical features.
Medicine [Internet]. 2020; 48(9):561-566. doi: https://doi.
org/gpzh7c
[10] Cavallaro U, Castelli V, Del Monte U, Soria MR. Phenotypic
alterations in senescent large-vessel and microvascular
endothelial cells. Mol. Cell. Biol. Res. Commun. [Internet].
2000; 4(2):117-121. doi: https://doi.org/fvgmc8
[11] Asai K, Kudej RK, Shen YT, Yang GP, Takagi G, Kudej AB, Geng
YJ, Sato N, Nazareno JB, Vatner DE, Natividad F, Bishop SP,
Vatner SF. Peripheral vascular endothelial dysfunction and
apoptosis in old monkeys. Arterioscler. Thromb. Vasc. Biol.
[Internet]. 2000; 20(6):1493-1499. doi: https://doi.org/fv6m7b
[12] Wang H, Listrat A, Meunier B, Gueugneau M, Coudy-Gandilhon.
C, Combaret L, Taillandier D, Polge C, Attaix D, Lethias C,
Lee K, Goh KL, Béchet D. Apoptosis in capillary endothelial
cells in ageing skeletal muscle. Aging Cell. [Internet]. 2014;
13(2):254-262. doi: https://doi.org/gcbqs9
[13] Dong L, Gan L, Wang H, Cai W. Age-Related impairment of
structure and function of iliac artery endothelium in rats is
improved by elevated fluid shear stress. Med. Sci. Monit.
[Internet]. 2019; 25:5127-5136. doi: https://doi.org/g832mj
[14] Liping D, Jia L, Guangyi L, Heng Y. [Effect of aging on the
ultrastructure of common iliac artery in rats]. Chinese J. Tiss.
Eng. Res. [Internet]. 2022; 26(26):4123-4126. Chinese. doi:
https://doi.org/g832mk
[15] Dymecka A, Walski M, Pokorski M. Ultrastructural degradation of
the carotid body in the aged rat: Is there a role for atherosclerosis
in the main carotid arteries? J. Physiol. Pharmacol. [Internet].
2006 [cited 24 Jun. 2024]; 57(Suppl.4):85-90. PMID: 17072033.
Available in: https://goo.su/VoAEp
[16] Wang M, Zhang J, Spinetti G, Jiang LQ, Monticone R, Zhao
D, Cheng L, Krawczyk M, Talan M, Pintus G, Lakatta EG.
Angiotensin II activates matrix metalloproteinase type II
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