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D Vesselinovitch

Publications and source records attributed to D Vesselinovitch.

At least 19 recordsLinked to original sources
PubMed1990

Can atherosclerotic plaques regress? Anatomic and biochemical evidence from nonhuman animal models.

For at least 60 years, spotty and poorly documented evidence has suggested that atherosclerotic disease in humans might be reversible. Little direct evidence was available until researchers demonstrated that rather advanced atherosclerotic lesions in experimental animals could show marked improvement after blood-lipid-reducing regimens that were often combined with other measures, such as increased ambient oxygen and estradiol therapy. In fact, this combination was used in this laboratory to produce one of the first effective regression studies in the rabbit model. In more recent studies in this laboratory, abundant evidence has been obtained that the advanced, eccentric, largely intimal lesions produced in the rhesus monkey are substantially reversible, and the much more inflammatory, concentric, and often transmural atheroarteritis induced by the same atherogenic ration in the cynomolgus monkeys is much more resistant to effective and beneficial regression. This unusual reaction appears to be due to the circulating immune complexes that participate in the pathogenesis of atherosclerosis in these cynomolgus monkeys, as well as possibly in a number of humans. The evidence for this phenomenon, as well as the varying effects of the lesions induced with contrasting food fats, is summarized in this presentation. Some of the time-related effects of varying interventions when the lesions are studied at 4-month intervals in rhesus and cynomolgus monkeys are also discussed. Other factors that may influence regression are also considered.

Animals↗
PubMed1990

An update on the pathogenesis of atherosclerosis (principles of prevention, intervention, retardation, and regression).

The major life-threatening ischemic events in heart and brain are precipitated by the plaque. Thrombosis in the muscular arteries and rupture of the large elastic arteries usually follows fracture or ulceration of the plaque's fibrous cap. The smooth muscle cell (SMC) participates in many aspects of the atherosclerotic process: lipid uptake, synthesis of plaque components, and cell proliferation. The latter is a particularly significant aspect of the disease. High serum cholesterol levels stimulate proliferation of arterial medical cells; lower-density lipoproteins (LDL and B-VLDL) induce ingress and storage of cholesteryl ester in the arterial intima. These effects are inhibited by high-density lipoproteins (HDL). Endothelial injury may be an important part of the pathogenesis of some atherosclerotic plaques because powerful growth factors liberated from circulating monocytes, injured endothelial cells, and platelets, actively stimulate SMC proliferation, even when other risk factors are absent.

Animals↗
PubMed1990

Aneurysm formation in experimental atherosclerosis: relationship to plaque evolution.

To determine whether aneurysms form in experimental diet-induced atherosclerosis, we reviewed our experience with cynomolgus monkeys (n = 268) and rhesus monkeys (n = 175) fed an atherogenic diet for various lengths of time. Many animals in long-term experiments were fed "regression" diets and cholestyramine to lower cholesterol levels after lesions were established. No aneurysms were found in animals on normal diet. There were no aneurysms in 252 animals fed an atherogenic diet with or without regression for 12 months or less. However, 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. Four of the five animals with aneurysms were on a regression diet and cholestyramine for 4 to 12 months. The fifth was fed the atherogenic diet for 20 months without subsequent regression. Aneurysms were prominent and involved the thoracic and abdominal aorta, innominate artery, carotid arteries, iliac and femoral arteries, and formed in areas most involved with plaque formation in both species. Histologic evidence was found of thinning of the media and atrophy with loss of normal architecture. The higher incidence of aneurysms in cynomolgus monkeys was associated with greater media destruction than was noted in the rhesus. These data support the thesis that aneurysm formation is a manifestation of atherosclerosis. In primate atherosclerosis, aneurysms form only after prolonged exposure to the atherogenic regimen, even in the presence of declining serum cholesterol levels. Matrix fibers in plaques may provide structural support to the aortic wall where there is underlying atrophy of the media. With time or declining serum cholesterol levels or both, plaques may atrophy leaving an aortic wall too thin to support increasing mural tension, leading to aneurysmal enlargement.

Animals↗
PubMed1989

Effects of feeding fish oil on the properties of lipoproteins isolated from rhesus monkeys consuming an atherogenic diet.

This study examined plasma lipids and lipoproteins of rhesus monkeys fed fish oil incorporated into a highly atherogenic diet containing saturated fat and cholesterol. The animals were fed diets containing 2% cholesterol and either 25% coconut oil (group I), 25% fish oil/coconut oil (1:1; group II), or 25% fish oil/coconut oil (3:1; group III) for 12 months (n = 8/group). Adding menhaden fish oil to the diet increased plasma eicosapentaenoic acid and docosahexaenoic acid and decreased plasma linoleic acid in animals fed the fish oil containing diets. Plasma concentrations of all lipoprotein fractions were decreased in the fish oil groups. VLDL isolated from group I animals exhibited beta-mobility on agarose gels but the VLDL from groups II and III animals did not. The group I VLDL was more highly enriched in cholesteryl ester than was VLDL from groups II and III. Group I LDL had a small but significant increase in cholesteryl ester content compared to group III LDL. No differences in HDL composition were observed in the 3 groups. At least 6 times less apo E was recovered in VLDL, IDL, and LDL from group III animals than from group I animals. Assuming 1 molecule of apo B per lipoprotein particle, there were 50% fewer VLDL, IDL, and LDL particles in group III than in group I animals. Group III also had significantly lower molar ratios of apo E/apo B in VLDL, IDL, and LDL than did group I animals. When VLDL from all 3 groups were incubated with J774 macrophages at equal protein concentrations, only the VLDL from the group I animals stimulated cholesterol esterification. Thus, introducing fish oil into an atherogenic diet reduced the number of VLDL, IDL and LDL particles in plasma by as much as 50%, reduced the cholesteryl ester content of the circulating lipoprotein, and reduced the ability of the VLDL to stimulate cholesterol esterification in macrophages.

Animals↗
PubMed1989

Suppression of atherogenesis by nifedipine in the cholesterol-fed rhesus monkey.

Diet-induced atherosclerosis in rhesus monkeys was suppressed in the carotid arteries and thoracic aorta by the calcium antagonist nifedipine given orally for a period of 1 year at a dose of 10 mg b.i.d. The extent of atherosclerosis was determined by quantitative micromorphometric studies. No change in serum blood cholesterol or biochemical composition of the major vessels was detected, but the intimal area and thickness of the atherosclerotic plaques in the carotid arteries of the nifedipine group were markedly less than those found with the control group (p less than 0.05). However, no statistically significant differences were seen in the degree of atherosclerotic involvement of the other major arterial vessels. Although the mechanism is not clear, nifedipine may be useful in the treatment of carotid artery disease.

Animals↗
PubMed1989

Plasma platelet factor 4 response in rhesus monkeys fed coconut oil.

Platelet factor 4 (PF 4), the low molecular weight polypeptide stored in the alpha granule, has been shown to be released from platelets during the process of activation. To examine the effects of known atherogenic food fats on platelet activation, as manifested in circulating PF 4 concentrations, groups of rhesus monkeys were fed diets enriched with varying quantities of different food fats. Plasma PF 4 levels were measured at set intervals during the experimental period. Platelet counts were performed and PF 4 values assayed using the radioligand binding technique. Animals given coconut-oil-enriched diets showed the greatest increase in PF 4 levels; while those fed corn, peanut and soybean-oil-containing rations showed small insignificant fluctuations of plasma PF 4 values. In this study the coconut oil effect on plasma PF 4 values increased with time; diluting the coconut oil with increasing quantities of corn oil led to progressive decreases in these values. These data indicate an increased incidence of platelet activation in animals fed coconut-oil-enriched diets, and suggest that corn oil counteracts this thromboactive effect of coconut oil.

Animal Feed↗
PubMed1988

Brief overview of the mounting evidence that atherosclerosis is both preventable and reversible.

The major life-threatening events in advanced atherosclerosis are precipitated by the plaque. Thrombosis in the muscular arteries and rupture of the large elastic arteries usually follows rupture of the plaque's fibrous cap. The smooth muscle cell (SMC) participates in many aspects of the atherosclerotic process: lipid uptake, synthesis of plaque components, and cell proliferation. The latter is a particularly significant aspect of the disease. High serum cholesterol levels stimulate proliferation of arterial medial cells; low-density lipoproteins (LDL) from hyperlipidemic plaques induce ingress and storage of cholesterol ester. These effects are inhibited by high-density lipoproteins (HDL). Endothelial injury may be an important part of the pathogenesis of some atherosclerotic plaques because powerful growth factors actively stimulate SMC proliferation, even when other risk factors are absent. Utilization of animal models of atherosclerosis, especially nonhuman primate models, has led to great progress in understanding this disease process. In controlled feeding experiments, severe atherosclerosis has been produced in rhesus monkeys by means of a high fat, high cholesterol diet. Animals then placed on a low fat, low cholesterol diet, or given cholestyramine, or a combination of these two approaches, showed a remarkable decrease in the size of their atherosclerotic plaques. Many epidemiologic studies, as well as more recent prospective intervention studies involving bile acid sequestrants, indicate by imaging techniques that plaque regression takes place in humans.

Arteriosclerosis↗
PubMed1988

Quantitative ultrastructural analysis of coronary atherosclerotic involvement in two macaque species.

Ultrastructural analyses were employed to observe and to compare in detail lesions of the coronary artery of cynomolgus and rhesus monkeys. Animals were fed individually with the same atherogenic ration under identical conditions for 4, 8, and 12 months, and controls of each species were fed with a low fat, cholesterol-free ration. Transmission electron microscopic studies of coronary arteries from these animals led to the following conclusions: (1) Synthetic smooth muscle cells (SMC) without lipid and macrophages without lipid appeared more frequently in the cynomolgus lesions than in the rhesus lesions. Furthermore, phenotypic expression of synthetic SMCs in the cynomolgus was more active with greater diversity, while the rhesus showed less phenotypic modulation. Macrophages without lipid appeared frequently in the cynomolgus media. (2) Increased percentages of both synthetic SMCs with lipid and macrophages with lipid were demonstrated in the cynomolgus lesions as compared to those in the rhesus. This indicates that foam cells, including SMC- and macrophage-derived foam cells, are more prevalent in cynomolgus than in rhesus. They are considered to play an important role in atherogenesis. (3) Medial disruption, synthetic SMCs, and macrophages containing lipid appeared more often in cynomolgus media than in rhesus media. (4) There were greater percentages of both synthetic SMCs and macrophages in the intima of the myocardial side of coronary arteries in both species. (5) Approximately 42% of all foam cells in the cynomolgus lesions were derived from SMCs. There were fewer macrophages in rhesus lesions. (6) The difference in expression between the two macaque species reflects different responses of macrophages to medial smooth muscle cell (SMC) components. The configuration of the artery wall could be one of the important indicators of these different expressions.

Animals↗
PubMed1988

Animal models and the study of atherosclerosis.

Identifications, requirements, and numerous contributions of animal models, as well as different aspects of atherosclerosis that were successfully studied in animals, are reviewed. Suggestions are made for updating the selection of specific animal models that will most satisfactorily fulfill the needs of studies in a particular problem of this disease process. Attention has been called to the importance of the type of atherosclerotic lesions and their dependence on species susceptibility and dietary influence. The role the type of lesion plays in atherosclerosis has been emphasized, especially in studies concerned with the progression and therapy of this disease process. From the variety of animals listed in this review, as well as the number of different problems already studied or awaiting further study, it appears that numerous data can be reconciled to help elucidate many problems and provide information for our better understanding of atherosclerosis. This, in turn, will allow us to make more accurate and effective recommendations leading to prevention and/or treatment of atherosclerosis.

Animals↗
PubMed1987

The sympathetic nervous system and atherosclerosis.

Morphometric and chemical changes in the arterial wall were studied after 12 months of diet-induced atherosclerosis in rhesus monkeys treated with either bilateral surgical thoracic sympathectomy or propranolol. There was a marked reduction in the progression of atherosclerosis in the carotid arteries and a moderate reduction in the disease found in the thoracic aorta of monkeys treated initially with a sympathectomy, in comparison to control monkeys fed an atherogenic diet alone. Propranolol at a dose of 40 mg/12 hrs also seemed to reduce the progression of atherosclerosis in the carotid arteries and thoracic aorta, although the differences were less dramatic. There were minimal differences in the extent of atherosclerosis in the abdominal aorta or femoral arteries of animals in either treatment group as compared with the control group. Similarly, the chemical composition of these same major vessels showed no significant differences. Therefore, in the face of severe atherogenic stimuli, chemical or surgical sympathectomy may be useful in controlling atherosclerosis in specific arterial beds.

Animals↗
PubMed1986

Ultrastructural aspects of cynomolgus atherosclerotic carotid artery lesions on cholestyramine 'regression' treatment.

The carotid artery lesions of atherosclerotic cynomolgus monkeys treated with cholestyramine and studied with scanning electron microscopy appeared to be less bulging and largely covered by endothelial cells. With transmission electron microscopy these lesions showed an evident disappearance of cells and of extra- and intracellular lipid; a marked relative increase of fibrous material in the intercellular matrix, chiefly collagen and elastin fibers, was noted.

Animals↗
PubMed1984

Reticuloendothelial system response to hyperlipidemia in rhesus and cynomolgus monkeys.

A detailed study of the effect of various periods of hyperlipidemia on the reticuloendothelial system (RES) lipid accumulation in rhesus and cynomolgus monkeys was conducted. The cynomolgus serum cholesterol and triglyceride levels were on the average more elevated than the rhesus levels throughout a 12-month period when both species were fed a diet containing 12.5% coconut oil, 12.5% butter fat, and 2% cholesterol. After cynomolgus monkeys were fed this diet, their reticuloendothelial system became more lipid laden than that of the rhesus monkeys, in both the liver and the spleen. This was also true for the circulating monocytes. Furthermore, the parenchymal cells of the cynomolgus livers also become more fat filled, and chemical analyses demonstrated more cholesterol (total, free, and esterified) and triglycerides in the liver and the spleen. Xanthomata development in the cynomolgus, although similar in type and distribution, was more extensive than that in the rhesus monkey after similar periods of experimental diet feeding. Therefore, the RES of two species of macaque monkeys are affected differently when challenged with the same high fat, high cholesterol diet, with the cynomolgus RES being much more involved with lipid and cholesterol storage than the rhesus RES.

Animals↗
PubMed1984

Experimental atherosclerosis in rabbits fed cholesterol-free diets. Part 12. Comparison of peanut and olive oils.

The atherogenicity of peanut oil is well established as is the fact that the structure of the component triglycerides of peanut oil influences its atherogenicity. This study was carried out to determine if the relative saturation of peanut oil was partly responsible for the observed effects. Rabbits were fed a semipurified, cholesterol-free diet containing 14% of North American peanut oil (iodine value, 100), South American peanut oil (iodine value, 110) or olive oil (iodine value, 83) for 8 months. Rabbits fed olive oil exhibited higher levels of serum and liver lipids than did the two peanut oil-fed groups but significantly lower levels of aortic atherosclerosis. The findings confirm earlier observations that the structure of a fat can have an affect on its atherosclerogenic potential that is independent of its level of unsaturation.

Animals↗
PubMed1984

Correlations of aortic histology with gross aortic atherosclerosis and metabolic measurements in diabetic and nondiabetic Macaca nigra.

We studied the aortic histology of 28 Macaca nigra males and females, from 6 to more than 20 years old, normal and manifesting various degrees of spontaneous diabetes. Correlations of several metabolic and hormonal indicators of diabetes severity with gross and microscopic findings in the aortas demonstrated direct associations with the severity of atherosclerosis. Mild to relatively severe aortic lesions were present. These monkeys showed many changes similar to those observed in medium and large arteries of diabetic humans. Intimal proliferation, prominent extracellular fibers as part of the intimal thickening, and lipid deposition--mostly in extracellular locations--were particularly evident. Significant relationships were observed when glucose clearance, insulin secretion, and fasting glucose levels were correlated with all aortic microscopic findings. Cholesterol concentrations had no correlation with the histological state of the aortas, and triglyceride levels correlated only with aortic lipid content and intimal thickness. Aortic pathologic changes increased with age; diabetics had significantly greater changes than nondiabetics. Macaca nigra can be useful in the study of how diabetes affects the development of atherosclerosis without the influence of an atherogenic diet.

Animals↗