Chronic intermittent mental stress promotes atherosclerotic plaque vulnerability, myocardial infarction and sudden death in mice

Abstract

Vulnerable atherosclerotic plaques are prone to plaque rupture leading to acute cardiovascular syndromes and death. Elucidating the risk of plaque rupture is important to define better therapeutic or preventive strategies. In the present study, we investigated the effect of chronic intermittent mental stress on atherosclerotic plaque stability and cardiovascular mortality in apolipoprotein E-deficient (ApoE(-/-)) mice with a heterozygous mutation in the fibrillin-1 gene (Fbn1(C1039G+/)(-)). This mouse model displays exacerbated atherosclerosis with spontaneous plaque ruptures, myocardial infarction and sudden death, when fed a Western-type diet (WD). Female ApoE(-/-)Fbn1(C1039G+/-) mice were fed a WD for up to 25 weeks. After 10 weeks WD, mice were divided in a control (n = 27) and mental stress (n = 29) group. The chronic intermittent mental stress protocol consisted of 3 triggers: water avoidance, damp bedding and restraint stress, in a randomly assigned order lasting 6 h every weekday for 15 weeks. Chronic intermittent mental stress resulted in a significant increase in the amount of macrophages in atherosclerotic plaques of the proximal ascending aorta, whereas type I collagen and fibrous cap thickness were decreased. The coronary arteries of mental stress-treated mice showed larger plaques, more stenosis, and an increased degree of perivascular fibrosis. Moreover, myocardial infarctions occurred more frequently in the mental stress group. As compared to the control group, the survival of stressed ApoE(-/-)Fbn1(C1039G+/-) mice decreased from 67% to 52% at 25 weeks WD, presumably due to myocardial infarctions. In conclusion, chronic intermittent mental stress promotes plaque instability, myocardial infarctions, and mortality of ApoE(-/-)Fbn1(C1039G+/-) mice.

Social stress shortens lifespan in mice

“…Having ruled out a critical role for common tumors as the more likely explanation for the social status difference in survival, we focused on cardiovascular diseases based on their established association with stress, aging, and senescence (Costoli et al., 2004; Roth et al., 2015). We analyzed heart samples of LCPS mice sacrificed at 17 months of age to determine occurrence of myocardial damage or atherosclerosis.…”

Everolimus depletes plaque macrophages, abolishes intraplaque neovascularization and improves survival in mice with advanced atherosclerosis

“…16 In the present study, we used a novel animal model of advanced atherosclerosis, namely ApoE −/− Fbn1 C1039G+/− mice 9 , to re-evaluate the effects of everolimus on pre-existing lesions and to determine whether everolimus can counter plaque vulnerability and reduce atherosclerosis-driven complications. Given that these complications can be accelerated in ApoE −/− Fbn1 C1039G+/− mice via hypertension and mental stress, 17,18 or reduced by cholesterol withdrawal and statin therapy, 19 this mouse model is a validated and valuable tool for testing pharmacological interventions. To assess the role of mTOR inhibition in attenuating plaque vulnerability, rather than plaque growth, mice received a WD for a period of 12 weeks before starting therapy.…”

Coronary calcinosis and psychological distress association, by the data from ESSE-RF study in Kemerovskaya Region

“…Поскольку сердечно-сосудистые заболевания являются ведущей причиной смертности, то понятен интерес к влиянию психосоциальных факторов на их возникновение. Известно негативное влияние хронического стресса на развитие и прогрессирование атеросклероза [2]. В эпидемиологических исследованиях было показано, что уровень гормонов стресса (в частности, кортизола) был ассоциирован с более высокими значениями кальциевого индекса (КИ) коронарных артерий [3].…”