Carotid artery atherosclerosis in cholesterol-fed female cynomolgus monkeys. Effects of oral contraceptive treatment, social factors, and regional adiposity.

Shively, Carol A.; Kaplan, Jay R.; Clarkson, Thomas B.

doi:10.1161/01.atv.10.3.358

Cited by 23 publications

(17 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although corrections for multiple comparisons were not made, we observed several novel relationships between behavioral and physiological risk factors and carotid artery atherosclerosis extent. In agreement with previous studies, 45,47 circulating cholesterol was the strongest predictor of atherosclerosis in all but the LIC. Instead LIC atherosclerosis extent was most strongly associated with echocardiographic measures, LV-IDD and AO-VTI.…”

Section: Discussionsupporting

confidence: 93%

“…28 Depressed monkeys are generally dyslipidemic, have decreased BWs and BMI, and develop greater coronary artery atherosclerosis than non-depressed monkeys 34 Carotid artery atherosclerosis pathogenesis has been described in this model 45,47 but the carotid artery atherosclerosis phenotype associated with depressive symptomology has not been previously studied. Use of this model provides for the unique opportunity to characterize comorbid depression and carotid artery atherosclerosis while simultaneously conducting a placebo-controlled long-term randomized trial in model well-suited for clinical translation.…”

Section: Discussionmentioning

confidence: 91%

See 1 more Smart Citation

Long-term sertraline treatment and depression effects on carotid artery atherosclerosis in premenopausal female primates

et al. 2017

View full text Add to dashboard Cite

Objective Atherosclerosis developed during premenopausal years predicts postmenopausal atherosclerosis burden. Selective serotonin reuptake inhibitor (SSRI) antidepressants, recently approved for hot flushes, have been associated with increased ischemic stroke risk in several observational studies; however effects on carotid artery atherosclerosis, a strong predictor of future vascular events, are unknown. Methods The effects of chronic administration of a commonly prescribed SSRI, sertraline HCl, on atherosclerosis in the carotid artery was assessed in a placebo-controlled, longitudinal, randomized study of premeonopausal depressed and nondepressed cynomolgus monkeys (Macaca fascicularis; n=42). Physiologic and behavioral phenotypes were evaluated at baseline and after 18-months of oral sertraline (20 mg/kg, n=21) or placebo (n=21). Carotid artery atherosclerosis was measured post-mortem via histomorphometry. Results Atherosclerosis extent in the right common carotid artery, on average, was 60% greater in sertraline-treated depressed monkeys compared to all other groups (p=0.028). The results of linear regression analyses suggested that sertraline and depression effects on atherosclerosis were not mediated by their effects on behavioral and physiological risk factors. Conclusions These findings suggest that chronic SSRI treatment is associated with the progression of carotid artery atherosclerosis, which may increase the risk for future vascular events, particularly in depressed women. The underlying mechanism remains to be determined, but does not appear to be related to SSRI effects on traditional cardiovascular risk factors.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 91%

Long-term sertraline treatment and depression effects on carotid artery atherosclerosis in premenopausal female primates

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Female cynomolgus monkeys that are stressed by social subordination have more abdominal fat (30,47,48). Furthermore, subordinate females have hypercortisolemia (46), dyslipidemia (15), tachycardia in response to stress (46), impaired ovarian function (1), and enhanced coronary and carotid atherosclerosis (1,49), all symptoms being consistent with the metabolic syndrome profile.…”

Section: Summary and Perspectivesmentioning

confidence: 99%

Social stress and recovery: implications for body weight and body composition

Tamashiro¹,

Nguyen²,

Ostrander³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

105

View full text Add to dashboard Cite

Social stress resulting from dominant-subordinate relationships is associated with body weight loss and altered body composition in subordinate (SUB) male rats. Here, we extend these findings to determine whether stress-induced changes in energy homeostasis persist when the social stress is removed, and the animal is allowed to recover. We examined body weight (BW), body composition, and relevant endocrine measures after one or two cycles of 14 days of social stress, each followed by 21 days of recovery in each rat's individual home cage. SUB lost significantly more BW during social housing in a visible burrow system (VBS) compared with dominant (DOM) animals. Weight loss during social stress was attributable to a decrease in adipose tissue in DOM and SUB, with an additional loss of lean tissue in SUB. During both 21-day recovery periods, DOM and SUB regained lost BW, but only SUB were hyperphagic. Following recovery, SUB had a relatively larger increase in adipose tissue and plasma leptin compared with DOM, indicating that body composition changes were dependent on social status. Control animals that were weight matched to SUB or male rats exposed to the VBS environment without females, and that did not form a social hierarchy, did not exhibit changes in body composition like SUB in the VBS. Therefore, chronic social stress causes social status-dependent changes in BW, composition and endocrine measures that persist after repeated stress and recovery cycles and that may ultimately lead to metabolic disorders and obesity.

show abstract

“…4) [Shively et al, 1987]. Later, these findings were replicated and extended to carotid artery atherosclerosis extent [Shively et al, 1990]. These were the first data to suggest that central fat deposition results in exacerbated atherosclerosis.…”

Section: Introductionmentioning

confidence: 93%

Social stress, visceral obesity, and coronary artery atherosclerosis: product of a primate adaptation

Shively

Clarkson

2009

American J Primatol

115

View full text Add to dashboard Cite

Abdominal obesity is prevalent and often accompanied by an array of metabolic perturbations including elevated blood pressure, dyslipidemia, impaired glucose tolerance or insulin resistance, a prothrombotic state, and a proinflammatory state, together referred to as the metabolic syndrome. The metabolic syndrome greatly increases coronary heart disease (CHD) risk. Social stress also increases CHD although the mechanisms through which this occurs are not completely understood. Chronic stress may result in sustained glucocorticoid production, which is thought to promote visceral obesity. Thus, one hypothesis is that social stress may cause visceral fat deposition and the metabolic syndrome, which, in turn increases CHD. CHD is caused by coronary artery atherosclerosis (CAA) and its sequelae. Cynomolgus monkeys (Macaca fascicularis) are a well-established models of CAA. Social subordination may be stressful to cynomolgus monkeys and result in hypercortisolemia and exacerbated CAA in females. Herein is reviewed a body of literature which suggests that social stress increases visceral fat deposition in cynomolgus monkeys, that subordinate females are more likely than dominants to have visceral obesity, that females with visceral obesity have behavioral and physiological characteristics consistent with a stressed state, and that females with high ratios of visceral to subcutaneous abdominal fat develop more CAA. While these relationships have been most extensively studied in cynomolgus macaques, obesity-related metabolic disturbances are also observed in other primate species. Taken together, these observations support the view that the current obesity epidemic is the result of a primate adaptation involving the coevolution with encephalization of elaborate physiological systems to protect against starvation and defend stored body fat in order to feed a large and metabolically demanding brain. Social stress may be engaging these same physiological systems, increasing the visceral deposition of fat and its sequelae, which increase CHD risk.

show abstract

Carotid artery atherosclerosis in cholesterol-fed female cynomolgus monkeys. Effects of oral contraceptive treatment, social factors, and regional adiposity.

Cited by 23 publications

References 39 publications

Long-term sertraline treatment and depression effects on carotid artery atherosclerosis in premenopausal female primates

Long-term sertraline treatment and depression effects on carotid artery atherosclerosis in premenopausal female primates

Social stress and recovery: implications for body weight and body composition

Social stress, visceral obesity, and coronary artery atherosclerosis: product of a primate adaptation

Contact Info

Product

Resources

About