Search PubMed⌕ Search

Biomedical subjects

T B Clarkson

Publications and source records attributed to T B Clarkson.

At least 91 records · Page 5Linked to original sources
PubMed1987

Mechanisms of atherogenesis.

Recently the nature of the cellular and molecular events in atherogenesis have been elucidated better. Some of these findings may be important in explaining individual differences in susceptibility to atherosclerosis that are independent of known risk factors. Nonhuman primates are valuable models for the study of mechanisms of diet-induced atherosclerosis. Cynomolgus macaques are useful for studies of male-female differences in atherosclerosis, since they share with premenopausal white women a relative protection against coronary atherosclerosis compared with males. These animals are also useful for psychosocial atherosclerosis research since social status affects the extent of atherosclerosis, and experimentally induced social stress increases extent of coronary artery atherosclerosis. Nonhuman primates have also been useful for studies of individual differences in susceptibility to diet-induced atherosclerosis and its risk factors. These studies have indicated that about 75% of the variability in the plasma cholesterol response to dietary cholesterol is attributable to genetically determined differences in cholesterol absorption and lipoprotein catabolism. There is preliminary evidence suggesting the existence of "mesenchymal susceptibility" in nonhuman primates; i.e., differences in risk of atherosclerosis that are independent of exposure to known risk factors. Efforts are being made to establish colonies of rhesus monkeys that possess contrasting degrees of mesenchymal susceptibility.

Animals↗
PubMed1987

Psychosocial influences on the pathogenesis of atherosclerosis among nonhuman primates.

Epidemiologic and clinical evidence derived from studies of human beings suggests that psychosocial phenomena may account for much of the variability in atherosclerosis extent and severity that is unexplained by the "traditional" risk factors (serum lipids, hypertension, and smoking). Animal preparations provide an opportunity to test hypotheses concerning the role of psychosocial phenomena in atherogenesis and to explore the mechanisms by which the effects of such phenomena are mediated. Here we review a relatively large series of studies of cynomolgus monkeys (Macaca fascicularis), a 5 kg animal having a complex social organization. The data indicate that, among male animals, individual behavior characteristics (social status and aggressiveness), physiologic responsiveness to psychological challenge, and stability of the social environment all interact to affect atherogenesis. Among female animals, individual patterns of aggressiveness appear to influence ovarian function, which in turn affects atherosclerosis. Future advances in the behavioral medicine aspects of atherogenesis are likely to arise through elucidation of the pathophysiologic pathways by which these behavioral responses and characteristics contribute to the events (endothelial injury, smooth muscle cell proliferation, lipid accumulation, calcification, and necrosis) associated with plaque pathogenesis. Such research can be pursued in studies utilizing nonhuman primates as well as in complementary studies involving human subjects.

Aggression↗
PubMed1986

Diet and vasectomy: effects on atherogenesis in cynomolgus macaques.

We report here the effect of a moderately atherogenic diet on the progression of atherosclerosis among cynomolgus macaques that were either vasectomized or sham vasectomized. Both groups were compared to sham vasectomized monkeys fed a control Monkey Chow diet. As expected, slight hyperlipoproteinemia induced by the moderately atherogenic diet increased endothelial cell replication rates and resulted in the development of intimal lesions among sham vasectomized monkeys. Unexpectedly, vasectomy resulted in reduced leukocyte adherence to arterial surfaces, reduced endothelial cell replication rates in response to the moderately atherogenic diet, and at most arterial sites, smaller intimal lesions were produced. These data suggest that with slight hyperlipoproteinemia vasectomy may result in a small protective effect against atherosclerosis, while other studies have shown that marked hyperlipoproteinemia in cynomolgus macaques along with vasectomy results in exacerbation of atherogenesis.

Animals↗
PubMed1986

Effects of age and/or puberty on coronary artery atherosclerosis in cynomolgus monkeys.

In this retrospective study of diet-induced atherosclerosis in male cynomolgus macaques, juvenile (2.5-3.5 years) and adult (6-12 years) monkeys that had consumed comparable atherogenic diets resulting in similar plasma lipid concentrations showed marked differences in coronary artery atherosclerotic lesion characteristics and extent. Adult animals (n = 16) developed more extensive lesions characterized predominantly as proliferative atherosclerotic plaques, while juveniles (n = 10) had minimal lesions that consisted primarily of fatty streaks. These differences in lesion characteristics and extent were not explained by differences in blood pressure. It is uncertain if these quantitative and qualitative differences in susceptibility to diet-induced atherosclerosis are due to intrinsic age-related changes in the arterial wall and/or related to the endocrine and metabolic changes associated with puberty. These findings may have relevance to the natural history of atherosclerosis in human beings.

Aging↗
PubMed1985

The effect of a menhaden oil-containing diet on hemostatic and lipid parameters of nonhuman primates with atherosclerosis.

Three species of nonhuman primates were fed an atherogenic diet for 6 months (baseline period) and a menhaden oil (EPA)-containing diet for 8 weeks (test period) during which various hemostatic and lipid parameters were compared. The EPA-rich diet prolonged bleeding times, inhibited platelet aggregation response to ADP and collagen, and increased mean platelet lifespan. This diet elicited an increase in the polyunsaturated fatty acids C20:5 (EPA) and C22:6 (docosahexaenoic acid) at the expense of C18:2 (linoleic acid) and C20:4 (arachidonic acid) in pooled samples of platelet membranes, creating an increase in the ratio of n-3/n-6 polyunsaturated fatty acids. The serum lipid response to a menhaden oil diet comprised a nonsignificant decrease in total serum cholesterol and a significant decrease in HDL cholesterol.

Animals↗
PubMed1985

Nonhuman primate models of atherosclerosis: potential for the study of diabetes mellitus and hyperinsulinemia.

Nonhuman primates have been used for many years to investigate the pathogenesis and progression of atherosclerosis. The use of these animal models has resulted in a better understanding of the risk factors associated with atherosclerosis. Nonhuman primates that have consumed an atherogenic diet for several years develop lesions that are comparable to those found in human beings. Diabetes, both spontaneous and chemically induced, has been described in a number of nonhuman primate species. These diabetic models may be used to understand the accelerated progression and vascular complications of atherosclerosis in diabetic human beings.

Animals↗
PubMed1985

The role of individual differences in lipoprotein, artery wall, gender, and behavioral responses in the development of atherosclerosis.

Striking individual differences exist in the response of animals to atherogenic diets. In this communication, we have summarized the accumulated data that relate to a better understanding of this individuality in susceptibility to atherosclerosis. Described herein, are the accumulated data concerning individual differences in the ways in which animals respond to dietary cholesterol. Also contained in this review, are beginning efforts to understand individual differences in susceptibility to coronary artery atherosclerosis at the level of the artery wall ("mesenchymal susceptibility"). We have placed special emphasis on individual differences that exist among cynomolgus macaques in certain psychosocial variables that contribute to individual differences in susceptibility. Among male cynomolgus macaques both status and social condition contribute to these individual differences. Additionally, individual differences in cardiovascular reactivity contribute to varying degrees of atherosclerosis development largely independent of plasma lipid concentrations. Among cynomolgus macaque females, stress-ovarian function relationships have a major influence on the relative degree to which these female animals are protected against diet-induced coronary artery atherosclerosis.

Animals↗
PubMed1985

Circulating immune complexes in cynomolgus macaques.

Nonhuman primates can be used as models for the study of immune-complex-associated diseases. Recognizing that very little is known about the levels of circulating immune complexes (CICs) in normal monkeys, we have used three assays to measure the levels in serum collected from 313 adult and 106 juvenile cynomolgus macaques (Macaca fascicularis). The prevalence was higher than expected. There was a strong statistical association between CIC levels and country of origin. Monkeys from Indonesia were more likely to have elevated CICs than those from Malaya or the Philippines. This relationship was observed with all three assays. Furthermore, juvenile macaques tended to have lower levels than did adults. This study indicates that it may be important to consider genetic factors, the country of origin, or both when selecting cynomolgus macaques for research on immune-complex-associated diseases.

Age Factors↗
PubMed1984

Psychosocial and reproductive influences on plasma lipids, lipoproteins, and atherosclerosis in nonhuman primates.

Until recently, research in experimental atherosclerosis focused primarily on nutritional influences on plasma lipids, lipoproteins, and atherosclerosis. We review here the results of recent studies of independent and interactive influences of psychosocial and reproductive influences on atherosclerosis in nonhuman primates. These studies have produced evidence that, as in human beings, individuals with certain personality characteristics who are frequently faced with stressful or challenging situations are at increased risk of coronary artery disease. Preliminary evidence suggests that this relationship may be mediated, in part, by heightened sympathetic arousal, i.e., cardiovascular hyperresponsiveness, to the environmental challenge. Also, as in human beings, evidence has been produced that certain negative behavioral and psychosocial variables can have a significant independent influence on plasma lipids. As regards reproductive influences, the cynomolgus macaque seems to share with premenopausal white women a relative protection against coronary artery atherosclerosis. This "female protection" against diet-induced atherosclerosis is abolished by ovariectomy, which also results in increased total plasma and low density lipoprotein (LDL) cholesterol concentrations. Subordinate social status also seems to abolish female protection in some individuals. Preliminary evidence suggests that subordinate females most liable to this loss of protection are those with apparent stress-induced chronic ovarian endocrine dysfunction, which, in turn, is associated with increased plasma LDL cholesterol and decreased plasma high density lipoprotein (HDL) cholesterol concentrations.

Animals↗
PubMed1984

A study of atherosclerosis regression in Macaca mulatta. V. Changes in abdominal aorta and carotid and coronary arteries from animals with atherosclerosis induced for 38 months and then regressed for 24 or 48 months at plasma cholesterol concentrations of 300 or 200 mg/dl.

Young adult male rhesus monkeys (Macaca mulatta) were fed an atherogenic diet for 38 months. After 38 months of atherosclerosis induction, a baseline group was selected and necropsied to determine the extent and severity of atherosclerosis before regression regimens were begun. The remaining animals were fed diets that varied in cholesterol concentration in order to maintain plasma cholesterol concentrations of approximately 200 or 300 mg/dl for either 24 or 48 months. The progression or regression of atherosclerosis in coronary arteries, abdominal aorta, and carotid arteries was determined by comparing them to the baseline group. Coronary artery atherosclerosis regressed in the majority of animals after 4 years but not after 2 years when plasma cholesterol concentrations were about 200 mg/dl. Among the animals maintained at plasma cholesterol concentrations of about 300 mg/dl, about half the animals progressed in the extent of coronary artery atherosclerosis while about half regressed. The majority of the animals that progressed in lesion extent were genetic hyperresponders to dietary cholesterol whereas those that regressed were predominantly hyporesponders, even though their plasma lipid concentrations were equivalent during the regression phase. The changes seen in atherosclerosis extent in the abdominal aorta were quite similar to the changes seen in coronary arteries. Changes at this site were not pronounced after 2 years, but after 4 years animals with plasma cholesterol concentrations of about 300 mg/dl progressed while the animals at 200 mg/dl were mostly unchanged. No evidence for atherosclerosis regression was found in the common carotid arteries or in the carotid bifurcations.

Animals↗
PubMed1984

Psychosocial influences on female 'protection' among cynomolgus macaques.

We evaluated atherosclerosis (coronary artery, aortic and carotid bifurcation), plasma lipids, and blood pressure in 15 male and 23 female cynomolgus macaques (Macaca fascicularis). In addition, female social behavior and ovarian function were monitored. The females lived in stable (unmanipulated) or unstable (periodically altered composition) social groups while males lived in stable groupings. All animals were fed for 30 months an atherogenic diet which resulted in moderate hyperlipoproteinemia (median total plasma cholesterol congruent to 275 mg/dl). Socially dominant females had less extensive and severe coronary artery atherosclerosis than males or socially subordinate females; atherosclerosis extent and severity were similar in these latter two groups. Importantly, dominant females also had regular ovarian function and relatively small adrenal glands while subordinate females had impaired ovarian function (increased frequency of anovulatory cycles and luteal phase deficiencies) and relatively large adrenal glands. The dominant and subordinate females did not differ in plasma lipids. These results suggest that female 'protection' from coronary artery atherosclerosis may be influenced as much by behavioral and hormonal characteristics as by plasma lipids. Among other findings, males had more extensive atherosclerotic lesions at the carotid bifurcations than females. In addition, males had lower high density lipoprotein cholesterol concentrations and higher blood pressures than females. The gender difference in extent of atherosclerosis at the carotid bifurcation was unrelated to social factors or plasma lipids; it may have been due, in part, to the higher blood pressures of the males.

Adrenal Glands↗
PubMed1984

5 alpha-Cholest-8(14)-en-3 beta-ol-15-one lowers serum cholesterol and induces profound changes in the levels of lipoprotein cholesterol and apoproteins in monkeys fed a diet of moderate cholesterol content.

5 alpha-Cholest-8(14)-en-3 beta-ol-15-one has been found to have significant hypocholesterolemic activity upon oral administration at a daily dosage of 75 mg/kg of body weight to Rhesus monkeys fed a diet of moderate cholesterol (Chol) content [0.19 mg/kcal (1 cal = 4.184 J) of diet]. The reductions in total serum Chol levels (mean, -41%) were associated with even more striking reductions (mean, -61%) in the levels of low density lipoprotein (LDL) plus very low density lipoprotein (VLDL) Chol and also with increases in high density lipoprotein (HDL) Chol levels (mean, +61%). The mean increase in HDL Chol was 33 mg/dl. In one animal, that with the lowest pretreatment HDL Chol level, the extent of the rise was 49 mg/dl (+120%). These changes were associated with reductions in the % of total serum Chol associated with LDL/VLDL, in the ratios of total Chol to HDL Chol and of LDL/VLDL Chol to HDL Chol, and in the levels of LDL protein. The 15-ketosterol also increased the % of total Chol associated with HDL, increased the level of HDL protein, and induced a shift in the HDL profile to one in which the HDL2 species was the predominant species. All of these changes are those generally considered desirable for the treatment and/or prevention of atherosclerosis.

Animals↗
PubMed1983

Social stress and atherosclerosis in normocholesterolemic monkeys.

Socially stressed adult male cynomolgus monkeys (Macaca fascicularis) fed a low fat, low cholesterol diet developed more extensive coronary artery atherosclerosis than unstressed controls. Groups did not differ in serum lipids, blood pressure, serum glucose, or ponderosity. These results suggest that psychosocial factors may influence atherogenesis in the absence of elevated serum lipids. Psychosocial factors thus may help explain the presence of coronary artery disease (occasionally severe) in people with low or normal serum lipids and normal values for the other "traditional" risk factors.

Animals↗