https://doi.org/10.52973/rcfcv-e34398
Received: 22/02/2024 Accepted: 01/06/2024 Published: 25/08/2024
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Revista Científica, FCV-LUZ / Vol. XXXIV, rcfcv-e34398
ABSTRACT
Atherosclerosis is the mechanistic basis of cardiovascular disorders
manifested by damage to the walls of the aorta, coronary, cerebral and
peripheral arteries, leading to the development of acute or chronic
ischemia of internal organs and tissues. This publication describes
a case of spontaneous atherosclerotic lesion of the aorta with the
formation of a dissecting aneurysm in an African green monkey male.
The ancestors were introduced from Ethiopia and Europe. The case
monkey was housed as a family group in an outdoor enclosure with
attached smaller room equipped with heating system. It lived 16.4
years. Pathological diagnosis was established through complete
autopsy and histopathology. Main disease was chronic atrophic
gastroenterocolitis in exacerbation complicated with alimentary
dystrophy, cachexia (brown atrophy of the myocardium, liver, skeletal
muscles). The concomitant diseases: complicated atherosclerosis
of the aorta, dissecting abdominal aortic aneurysm with a large
cylindrical organized thrombus in the aneurysm area, stenosing
atherosclerosis of the renal arteries, vascular wrinkled left kidney;
focal atherosclerosis of the coronary arteries and their branches with
small foci of atherosclerotic cardiosclerosis and arteriosclerosis
of cerebral arteries. The revealed changes indicate a signicant
similarity in the pathomorphogenesis of atherosclerotic lesions
in African green monkey and humans. It allows us to consider this
genus of primates as a promising laboratory model for studying
the pathogenesis and mechanisms of regression as well as the
effectiveness of therapeutic approaches to the treatment of
atherosclerosis and its complications.
Key words: Atherosclerosis; aneurysm; kidney diseases; primates;
monkeys
RESUMEN
La aterosclerosis es la base mecánica de los trastornos
cardiovasculares, que se maniestan en el daño a las paredes de
la aorta y las arterias coronarias, cerebrales y periféricas, lo cual
lleva a la isquemia aguda o crónica de órganos y tejidos internos. La
publicación describe un caso de lesión ateroesclerótica espontánea
de la aorta, con la formación de un aneurisma disecante en un mono
verde africano macho. Los antepasados fueron introducidos desde
Etiopía y Europa. El mono descrito en este estudio de caso fue alojado
por un grupo familiar en un recinto al aire libre con una habitación
adjunta más pequeña equipada con un sistema de calefacción.
Vivió 16,4 años. El diagnóstico patológico se estableció mediante
autopsia completa e histopatología. La enfermedad principal fue
gastroenterocolitis atróca crónica con exacerbación complicada
con distroa alimentaria, caquexia (atroa parda del miocardio,
hígado y músculos esqueléticos). Las enfermedades concomitantes:
aterosclerosis complicada de la aorta, aneurisma disecante de la
aorta abdominal con un gran trombo cilíndrico organizado en la zona
del aneurisma, aterosclerosis estenosante de las arterias renales,
riñón izquierdo vascular arrugado; aterosclerosis focal de las arterias
coronarias y sus ramas con pequeños focos de cardiosclerosis
aterosclerótica y arteriosclerosis de las arterias cerebrales.
Los cambios detectados indican una similitud signicativa en la
patomorfosis de las lesiones ateroescleróticas en el mono verde
africano y en los humanos. Esto nos permite considerar este género
de primates como un modelo de laboratorio prometedor para estudiar
la patogénesis y los mecanismos de regresión, así como la ecacia
de enfoques terapéuticos para el tratamiento de la ateroesclerosis
y sus complicaciones.
Palabras clave: Arteriosclerosis; aneurisma; enfermedades renales;
primates; mono
A complicated form of spontaneous aortic atherosclerosis in an African
green monkeys (Chlorocebus aethiops sabaeus) male
Clinical case
Forma complicada de ateroesclerosis en un macho de mono verde africano
(Chlorocebus aethiops sabaeus)
Caso clínico
Sergey Orlov
1,2
, Andrey Panchenko
2
* , Viktor Shestakov
3
, Artem Oganesian
3
, Yulia Kolesnik
1,3
, David Ilyazyants
3
, Elena Radomskaya
3
,
Tamara Fedotkina
1
, Dmitry Bulgin
3
, Leonid Churilov
1
1
Saint Petersburg State University, Laboratory of the Microangiopathic Mechanisms of Atherogenesis. Saint Petersburg, Russian Federation.
2
National Research Centre «Kurchatov Institute», Kurchatov Complex of Medical Primatology, Department of Molecular Biology. Sochi, Russian Federation.
3
National Research Centre «Kurchatov Institute», Kurchatov Complex of Medical Primatology, Department of Pathology. Sochi, Russian Federation.
*Corresponding author: ando.pan@gmail.com
TABLE I
Closest relatives of the Proband
Inventory No Kinship Date of birth Date of death
Longevity,
years
35138 Proband 27/05/2003 03/11/2019 16.4
1500 Mother 14/05/1984 09/01/2006 21.7
32108 Father 27/09/1995 23/08/2007 11.9
34368 Brother 13/06/2001 30/10/2012 11.4
36246 Brother 20/06/2005 09/01/2006 0.6
40386 Child, male 22/10/2012 31/07/2014 1.8
44260 Child, female 18/07/2017 alive
5 years old at
the study time
45403 Child, male 12/11/2018 alive
4 years old at
the study time
TABLE II
Body weight of Proband in dierent periods of life
Date 12/08/2003 19/10/2006 09/06/2017 03/11/2019
Age, years
0.2 3.4 14.0 16.4
Body weight, kg
0.4 3.8 6.7 3.8*
Reference body weight
range for males, kg [
15]
0.4–1.2 5.0–7.8 6.6–10.6 7.3–9.2
*: Body weight at autopsy
Aortic atherosclerosis in an African green monkeys / Orlov et al. ___________________________________________________________________
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INTRODUCTION
Atherosclerosis is the main cause of morbidity and mortality of
patients with cardiovascular disease which is caused by damage
to the coronary, cerebral and peripheral arteries, leading to the
development of heart attacks, strokes, and ischemic organ damage [1,
2, 3]. Initial atherosclerotic lesions are detected already in the second
decade of a human life. However, obvious clinical manifestations
usually appear many decades later [4, 5]. The pathomorphological
substrate of atherosclerosis includes in early stages fatty dots
and streaks, but later atheromas (lipid and brous atherosclerotic
plaques) appear in the arterial wall. Hence, the complicated course
of the latter with calcication, rupture and thrombosis, intraplaque
hemorrhages, fragmentation, and weakening of the vascular wall
leads to obvious clinical manifestations. They depend on progressing
vascular wall rigidity, narrowing of the arterial lumen (due to thrombi
and spasms caused by vasoconstriction autacoids generated by
unstable atheroma), embolism and aneurysms [4, 5, 6]. Both
environmental factors and genetic predisposition contribute greatly
to the development of atherosclerosis [5, 6, 7].
Atherosclerosis is observed in animals also. Some animal species,
including rabbits (Oryctolagus cuniculus), pigs (Sus scrofa domesticus),
and monkeys (New World monkeys: Saimiri spp., Callithrix spp.; Old
World monkeys: Macaca mulatta, Macaca fascicularis, Papio spp.,
Chlorocebus aethiops ssp.), are well–established laboratory models
of atherosclerosis, while others, such as dogs (Canis lupus familiaris),
hamsters (Cricetinae), mice (Mus musculus), rats (Rattus norvegicus),
cats (Felis catus), guinea pigs (Cavia porcellus), are less susceptible to
developing atherosclerosis and have been used to a lesser extent or
after genetic modications and/or under certain additional conditions
only [8, 9, 10]. Among them, a special place is occupied by nonhuman
primates, which have the greatest phylogenetic similarity with
humans compared to other species [9, 10]. Nonhuman primates
were extensively used to study dietary (high fat, high cholesterol,
etc.) induced atherosclerosis and are well characterized as the model
[10]. However, there is an alternative point of view, according to which
the atherosclerotic lesions in humans and most of animals have a
completely different etiology, pathogenesis, a different macroscopic
appearance and location/distribution within the arteries, as well as
different structure of the brous capsule [11].
Publications about the manifestations of spontaneous
atherosclerosis in animals exist but are rare [12, 13]. Thus, in dogs,
spontaneous atherosclerosis is rarely registered, with one study
reporting it only in 30 out of 6300 dogs (0.5%, autopsy data). Among
the affected dogs, sixteen had normal serum cholesterol levels
without any identied endocrinopathies, suggesting a role for some
other factors in the development of spontaneous atherosclerosis in
them [14]. Therefore, descriptive studies of the manifestations of
spontaneous atherosclerosis in animals are of signicant value for
the formation of the true concept on the etiology and pathogenesis
of this disease in both humans and animals.
The paper presents case of a pathomorphological study of a
Chlorocebus aethiops sabaeus male monkey with spontaneous
complicated form of aortic atherosclerosis: a widespread
atherosclerotic lesion of the aorta with the formation of a dissecting
aneurysm, stenosing atherosclerosis of the renal arteries and a
vascular wrinkled kidney.
MATERIALS AND METHODS
Animals
The study was performed on archival (study of autopsy reports)
and current pathological and clinical veterinary material of the family
(TABLE I) of African green monkeys (Chlorocebus aethiops sabaeus).
Proband – male inv. No. 35138 was born on May 27, 2003, healthy,
full–term, but small for date (TABLE II). Throughout his life, it was
healthy according to regular veterinary examinations. At the age
of 6 years, on November 24, 2009, it was treated for a laceration of
the scalp (blood test dated November 27, 2009 – red blood cells 3.8
× 10
12
·L
-1
, white blood cells 5.1 × 10
9
·L
-1
, erythrocyte sedimentation
rate 8 mm/h), was discharged from veterinary unit on December 12,
2009 being clinically healthy. It died on November 3, 2019 at the age
of 16.4 years. At the time of death, the emaciation was registered.
Husbandry
The colony of African green monkeys of Kurchatov Complex
of Medical Primatology (formerly Research Institute of Medical
Primatology, Sochi, Russia) accounts 42 male and 90 female monkeys.
The Proband family originated from Ethiopia and Europe. The Proband
belongs to second generation born in the colony after introduction
of originating monkeys. The Proband family was housed as group in
outdoor enclosure with 9 m
2
oor area and 2.75 m high fenced with
metal mesh and attached smaller room equipped with heating system
FIGURE 1. Close–up of a pathological specimen and microphotographs of
atherosclerotic changes in the aorta. A: Gross specimen of the abdominal aorta
and kidneys with atherosclerotic dissecting aneurysm and large cylindrical
organizing thrombus. B: Vascular wrinkled left kidney (“small red kidney”). C:
Aortic wall of abdominal region. Atherosclerotic plaque. Cleavage of the internal
elastic membrane, fragmentation of its bers, swelling of individual sections
of the elastic ber, H&E staining, 50×. D: Higher magnication of C, 400×, the
structure of vascular wall is completely lost at plaque boundary with calcium
deposits in the aortic wall (indicated with an arrows)
A B
C D
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to provide protection from bad weather and during the cold season.
The animals were fed standard pelleted breeding diet prepared
according to the Altromin (Lage, Germany) technique. The pelleted
base diet was enriched with fresh vegetables, fruits. Tap water was
available ad libitum.
Pathomorphological investigation
The Proband animal was subjected to a complete autopsy. Tissue
samples were fixed in 10% neutral formalin solution, standard
histological processing of the material was carried out in isopropyl
alcohol, followed by embedding in HISTOMIX paran medium (LLC
BioVitrum, St. Petersburg, Russia). Tissue sections 5–7 μm thick were
prepared and stained with hematoxylin and eosin (H&E). Morphological
analysis was performed on a biological microscope AXIO LAB.A1 (Carl
Zeiss Microscopy GmbH, Germany) with digital camera Axiocam 105
color (Carl Zeiss Microscopy GmbH, Germany).
Blood analysis
Blood samples were taken at morning from fasted animals without
sedation from the brachial vein into vacuum tubes with K
2
EDTA
or clotting activator with separation gel. Hematological analysis
was performed on a HumaCount 30TS analyzer (Human, Germany).
Biochemical analysis of blood serum was performed on a Cobas
6000 analyzer (Roche Diagnostics International Ltd, Switzerland)
using commercial kits.
RESULTS AND DISCUSSION
Detailed pathological diagnosis was established for the Proband:
The main disease was chronic atrophic gastroenterocolitis, in
exacerbation. Complications of the underlying disease were:
alimentary dystrophy, cachexia (brown atrophy of the myocardium,
liver, skeletal muscles); with the concomitant diseases: complicated
atherosclerosis of the aorta, dissecting abdominal aortic aneurysm
with a large cylindrical organized thrombus in the aneurysm area,
stenosing atherosclerosis of the renal arteries, vascular wrinkled
left kidney; focal atherosclerosis of the coronary arteries and their
branches with small foci of atherosclerotic cardiosclerosis and
arteriosclerosis of cerebral arteries.
Gross anatomical examination revealed that the intima of the
aorta was light yellow in color, with gray–yellow spots, stripes and
plaques in the thoracic and abdominal portions. In the abdominal
aorta, there was an intimal defect with blood penetration into the
degeneratively changed media, forming an intramural hematoma
with longitudinal dissection of the aortic wall and formation of a
large cylindrical thrombus with the signs of its organization. The
aneurysmal expansion in this area is clearly visible both on the native
preparation and after xation of the preparation (FIG. 1).
Gerota’s fasciae of both kidneys were hardly removable, exposing
uneven, ne–grained gray–red surfaces. On section, the kidneys were
gray–red in color, with the boundaries of the cortical and medulla
layers poorly distinguishable. The left kidney was signicantly reduced
in size (2.5 × 1.8 × 0.9 cm). The right one was 5.0 × 3.5 × 2.0 cm in size.
Pathohistological examination revealed atherosclerotic changes
in the coronary arteries (FIG. 2a–b), perivascular cardiosclerosis and
hypertrophy, combined with granular degeneration of cardiomyocytes
(FIG. 2c), kidney glomerulosclerosis (FIG. 2 d), arteriosclerosis of cerebral
vessels (FIG. 2e–f). In the coronary artery (FIG. 2 b), all layers demonstrated
an altered histoarchitectonics. The intima with endothelium and a
relatively wide subendothelial layer had an uneven surface protruding
into the vessel lumen. The subendothelial layer was poorly dened.
The media consisted of the circular bundles of smooth muscle cells.
Collagen bers of the loose brous connective tissue of the adventitia
were oxyphilic. The vasa vasorum were located in the adventitia. Clearly,
the proliferation of connective tissue is a direct continuation of the inner
layer of the intima with the involvement of the media.
Family anamnesis of the Proband was available. The closest
relatives of Proband, according to archival data of anatomical
pathology department, also suffered from several inammatory and
metabolic diseases. The mother of Proband, who lived for 21years,
was diagnosed with catarrhal colitis, amyloidosis of the liver and
kidneys. The father, who lived for 11 years, died of cirrhosis of the
liver, and chronic atrophic gastritis which was also established as
the concomitant disorder. Proband had two brothers: a male inv.
No. 34368 that lived for 11 years (the cause of its death was acute
enterocolitis) and male inv. No. 36246, who died of pneumonia in early
childhood, being just 7 months old. Proband had offspring (3animals).
These are: a male inv. No. 40386 lived – 1.8 years, died of pneumonia
FIGURE 2. Microphotographs of the arteries and kidney. A: The anterior interventricular supercial branch of the left coronary artery (ramus interventricularis anterior arteriae
coronariae sinistrae). Uneven thickening of the vessel wall, moderately severe coronary atherosclerosis, H&E staining, 100×. B: Higher magnication of A, 200×, the intima with
endothelium and a relatively wide subendothelial layer has an uneven surface protruding into the vessel lumen. C: The anterior wall of the left cardiac ventricle. Perivascular
cardiosclerosis and hypertrophy, combined with severe granular degeneration of cardiomyocytes. H&E staining, 200×. D: Right kidney. Glomerulosclerosis. Focal lymphocytic
inltration in the stroma, H&E staining, 200×. E: Prominent arteriosclerosis of the walls of the vessels of the brain tissue substance – uneven thickening, splitting of the walls
and narrowing of the lumen of the vessels. H&E staining, 100×. F: Higher magnication of E, 400×, compaction and thickening of the artery wall due to growth of brous tissue
A
B
C
D E F
TABLE III
Data of hematological and biochemical analysis of blood of Proband’s descendants
Index
The examined animals Reference values (x̄ ± SD)
Inv. No. 44260, female Inv. No. 45403, male females males
White blood cells × 10
9
·L
-1
13.44 6.80 8.10 ± 3.32 ¥ 6.15 ± 1.97 ¥
Red blood cells × 10
12
·L
-1
5.79 7.30 5.61 ± 0.64 ¥ 6.18 ± 0.57 ¥
ALT, U·L
-1
62.10 24.70 19.54 ± 14.23 ¥ 28.44 ± 14.74 ¥
AST, U·L
-1
41.70 26.10 27.88 ± 16.71 ¥ 33.40 ± 24.31 ¥
Alkaline phosphatase, U·L
-1
201.00 94.00 312.56 ± 168.36 ¥ 259.02 ± 108.04 ¥
Urea, mmol·L
-1
(urea nitrogen, mg·dL
-1
) 5.80 (16.2 mg·dL
-1
) 7.50 (21.0 mg·dL
-1
) 20.1 ± 5.1 mg·dL
-1
§ 19.8 ± 4.4 mg·dL
-1
§
Triglycerides, mmol·L
-1
1.61 (142.5 mg·dL
-1
) 0.39 (34.5 mg·dL
-1
) 46.5 ± 18.1 mg·dL
-1
§ 38.7 ± 15.4 mg·dL
-1
§
Cholesterol total (A), mmol·L
-1
4.71 (182.09 mg·dL
-1
) 3.54 (136.86 mg·dL
-1
)
127.79 ± 18.49 mg·dL
-1
¥
131.7 ± 18.9 mg·dL
-1
§
124.47 ± 15.76 mg·dL
-1
¥
114.9 ± 18.4 mg·dL
-1
§
Cholesterol HDLP (B), mmol·L
-1
2.23 2.42 – –
Cholesterol LDLP (C), mmol·L
-1
1.75 0.94 – –
Atherogenic coecient = (A-C)/B 1.11 0.46 – –
¥:data for females aged 3–4 years and for males aged 5–6 years [16], §:data for animals weighing from 1.5 to 7.5 kg without indicated age [17], data in
parentheses have been converted from mmol·L
-1
to mg·dL
-1
.
Aortic atherosclerosis in an African green monkeys / Orlov et al. ___________________________________________________________________
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and 2 more descendants alive at the time of the study: inv. No. 44260,
a female, age at the time of the study – 5 years and inv. No. 45403, a
male, age at the time of the study – 4 years. Both living descendants of
Proband are clinically healthy. They were subjected to blood sampling
for hematological and biochemical tests (TABLE III).
The analysis of lipid prole showed that the daughter of Proband
had a severe hypertriglyceridemia – 142.5 mg·dl
-1
, while the reference
data for a population comparable in age and sex are 46.5 ± 18.1 mg·dl
-1
.
Total cholesterol level (182.09 mg·dL
-1
) was above upper limit of
reference values.
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African green monkeys, also called “vervets” or “grivets”, include
several closely related species, are characterized by a lifespan in
captivity of up to 32 years. Females reach sexual maturity at 2 years,
and males at 5 years. African green monkeys appear to have a moderate
prevalence of spontaneous atherosclerosis in the form of aortic fatty
dots and streaks. Thus, out of 61 adults, fatty streaks were found in
48%, and among 21 adolescents, in 14%. The foci were characterized
by a diameter up to 2 mm, and were localized around the orices of the
branches of the vessels [18]. According to internal data in the colony
of African green monkeys of the institution, the atherosclerosis was
found in 33% of autopsies of animals over the age of 15 years of both
sexes. Main ndings were aortic fatty dots and streaks.
Many species of nonhuman primates develop atherosclerosis in
a way similar to that in humans. So, the lesions develop rst in the
abdominal aorta, and then in the thoracic aorta subsequently affecting
the proximal sections of the main branches of the epicardial coronary
arteries, the common carotid arteries, and nally the cerebral arteries
[10]. African green monkeys are susceptible to the development of
atherosclerosis when fed the diets with a relatively high amount of
cholesterol (0.5–0.8 mg·kcal
-1
) for a long time (3–5 years). At the same
time, diet–induced atherosclerotic lesions in African green monkeys
can be complex, and morphologically and biochemically are quite
similar to those in humans [10]. The development of lesions occurs
approximately twice as intensively in the abdominal portion of aorta
than in the thoracic one. Atherosclerosis of the coronary arteries mainly
occurs in the proximal sections of the main coronary arteries [10].
The development of the atherosclerotic process in Proband
corresponds to the pattern described above according cited
references. In the study, Proband showed a pronounced lesion of
the abdominal aorta with an atherosclerotic dissecting aneurysm,
a large cylindrical organizing thrombus and a vascular wrinkled left
kidney due to atherosclerotic damage to the orice of the renal artery.
Less pronounced atherosclerotic changes were in the thoracic aorta
and coronary arteries. Arteriosclerosis of cerebral arteries also was
found and probably indicates age–related pathology.
The pathomorphological picture of the aneurysm revealed in Proband
is similar to that described in humans. Thus, local expansion of a part
of the vascular wall is associated with type IV, V, and VI atherosclerotic
lesions in humans. Distinct localized external bulges or vascular
aneurysms are usually associated with type VI lesions in which the
intimal surface is highly eroded. Aneurysms often contain parietal
thrombi, both fresh and remnants of old ones. With long–existing
aneurysms, thrombotic deposits are usually layered, thrombolysis
or thrombi intramural inclusion due to collagen organization are
uncommon [19]. Spontaneous bleeding and rupture of the vessel wall
is considered an extremely rare phenomenon in large animal models
of atherosclerosis and have only been described in coronary arteries
of pigs with hereditary LDL hypercholesterolemia or in pigs fed with
cholesterol along with streptozotocin–induced diabetes [20, 21].
Formation of aneurysms in experimental diet–induced
atherosclerosis was reported in cynomolgus and rhesus monkeys.
Aneurysms formed in 13% of cynomolgus monkeys (4 of 31) and 1%
(1 of 107) rhesus monkeys on an atherogenic regimen for 16 to 24
months [22]. However, these ndings were criticized as authors did
not demonstrate aneurysmal dilation in any animal but rather, they
reported an increase in the cross–sectional area of the abdominal
aortic lumen at one specic site [23].
African green monkeys may be considered as a unique model for
spontaneous human atherosclerosis, even among the other nonhuman
primates. So, when comparing the metabolism of lipoproteins and
their size in rhesus monkeys, cynomolgus monkeys and African green
monkeys fed with atherogenic diet with human beings it is in African
green monkeys that the change in the lipoprotein prole and the size
of lipoproteins is closest to that in humans [10]. Also, effects of diet
enriched in saturated fat, monounsaturated fat or polyunsaturated
fat on plasma lipoproteins was similar to those seen in humans in
this nonhuman primate model [24]. Compared to squirrel monkeys
and macaques, African green monkeys have only small increase in
liver cholesterol content after long–term feeding of atherogenic
diets [25, 26].
It is well known that there are signicant individual differences in
the development of atherosclerosis under identical conditions in all
animal models, including monkeys. The plasma cholesterol response
to atherogenic diets among primate species can be low, moderate,
or high [27]. This individual variability is thought to be primarily due
to genetic factors [10].
In addition, there are signicant sex differences in the progression
rates of atherosclerosis in African green monkeys. Thus, the area of
atherosclerotic plaques in the coronary arteries was signicantly
larger in male than in female monkeys after 5 years of eating a
cholesterol–containing diet, enriched with either saturated or
polyunsaturated fats. Female monkeys fed a polyunsaturated fat
diet showed no signs of coronary artery atherosclerosis [28]. This
fact has been linked to the protective effect of estrogens [29].
An important factor determining the development of
atherosclerosis in monkeys is the sociopsychological one. Thus,
in social groups in dominant females of long–tailed macaques fed
with a high cholesterol diet, the development of atherosclerosis
actually not observed, and in subordinate individuals of a lower rank,
atherogenesis was at the level observed in males, and in such females
the hypercortisolemia, behavioral dysfunction and impaired ovarian
function were detected [29].
The presence of endocrinopathy is also an important factor
contributing to atherogenesis in animals. When streptozotocin–
induced diabetes mellitus was combined with the use of high
cholesterol diet in Yorkshire pigs, a 2–fold increase in the risk of
atherosclerosis was observed compared with a use of high cholesterol
diet alone. The development of atherosclerotic lesions in the aorta,
coronary and femoral arteries also accelerated [9]. First successful
attempt to obtain atherosclerosis model in carnivores (dogs) was
achieved only after high cholesterol diet in them was combined with
hypothyroidism [30].
African green monkeys develop abdominal obesity associated
with changes in insulin sensitivity and plasma lipid prole, thus
clearly demonstrating interactions between metabolic syndrome
and cardiovascular diseases [31]. There is also evidence on more
severe cardiovascular lesions in nonhuman primates infected with
SIV and fed with high–fat diet. Still in African green monkeys SIV
infection is nonpathogenic but was exacerbated by high–fat diet
[32]. Trimethylamine–N–oxide, a microbial choline metabolism
byproduct that is processed in the liver and excreted into circulation,
was shown to be involved in the control of atherosclerosis in African
green monkeys via miR–146–5p pathway [33]. A study utilizing
novel computational approach using individually expression data
demonstrated that immune cells, adipocytes, cardiomyocytes,
Aortic atherosclerosis in an African green monkeys / Orlov et al. ___________________________________________________________________
6 of 7
and smooth muscle cells played a synergistic role in cardiac and
physical functions in the aged female African green vervet monkeys
by regulation of the biological processes associated with metabolism,
inammation, and atherosclerosis [34].
There are no data on the social status of Proband and the presence
of some endocrine pathology in it. In terms of nutrition, all the animals
were kept on the same balanced base diet with addition of vegetables
and fruits. This makes it possible to exclude the role of the nutritional
factor in the development of atherosclerosis in Proband. To evaluate
the role of the hereditary factor the available pathomorphological
and laboratory studies data of the Proband’s relatives were assessed.
There were no data on atherosclerotic process among the deceased
relatives. Living children of Proband have no clinical signs of obesity
and glucose metabolism disorders. The female descendant of
Proband alive at the time of the study had an increase in blood level
of triglycerides (three times higher than the reference level) and of
total cholesterol, which suggests the role of a hereditary factor.
CONCLUSION
Spontaneous atherosclerosis in African green monkeys can
develop into pronounced clinical forms. The similarity of the
pathomorphological pattern of atherosclerosis and its complications
between African green monkeys and humans suggests that this
species of primates may be a valuable model for evaluating the
pathogenesis and mechanisms of regression, as well as the
effectiveness of therapeutic interventions in atherosclerosis.
Availability of data and materials
All data is within the manuscript and available on request from the
corresponding author.
Conict interests statement
The authors declare that they have no conicting interests.
Informed consent
The conditions for conducting the study on animals corresponded
to the standards of the Bioethical Committee of the Federal State
Budgetary Scientic Institution “RIMP”, approved on the basis of the
legal acts of the Russian Federation (GOST 33218–2014. Guidelines
for accommodation and care of laboratory animals. Species–specic
provisions for nonhumane primates doi: https://protect.gost.ru/
document.aspx?control=7&id=202272; Model law on the treatment of
animals. Resolution of the plenary meeting of the Interparliamentary
Assembly of the CIS Member States No. 29 dated 10/31/2007 doi:
https://docs.cntd.ru/document/902092614?marker) and the
requirements of the European Convention for the Protection of
Vertebrate Animals Used for Experiments or Other Purposes, ETS
No. 123. For this article the archival material on animals was used.
Blood samples were obtained as part of general veterinary health
monitoring and prevention examinations. Additional approval of the
study by the Institutional Bioethical Committee was not required.
Funding
This work was supported by the grant of the Government of the
Russian Federation for state support of scientic research carried
out under the supervision of leading scientists, agreement Nº 075–15–
2022–1110 dated 30 June 2022.
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