SUN-562 Long-Term Mental Stress Implications to Cardiovascular Disease in an Aged Mouse Model

Abstract

While clinical evidence indicates that exposure to mental stress is a linked to a two-fold increased risk for coronary heart disease, even independently from traditional risk factors, the underlying direct mechanisms between psychological stress and cardiovascular health status has not been determined. A growing aging population of adults 65 and older represents a particular patient population vulnerable to chronic mental stressors due to a decline in normal physiologic functions. The decrease in function of the cardiovascular system that occurs during aging leads to the activation of pathological processes associated with an increased risk for heart disease. Using a mouse model of mental stress induced by restraint, we mimic the biochemical and physiologic changes observed in chronically stressed humans, which is characterized by an increase in circulating glucocorticoids, such as cortisol. Middle-aged mice (6 months old) as well as old-aged mice (18 months old) were used to differentiate the effects of aging on the burden of mental stress associated cardiovascular disease. Genes implicated in cardiomyopathy and CVD were found to be significantly up-regulated, not only immediately after a two-week stress period, but remained significantly up-regulated after the mice were allowed to recover stress-free for 5 weeks. Gene expression of the glucocorticoid receptor was down-regulated following exposure to chronic stress, suggesting an involvement of the hypothalamic-pituitary axis negative feedback loop. Gene expression of markers for hypertrophy (MHY7, ACTA1, NPPB) were upregulated and persisted in upregulation after mice were allowed to recover. Hypertrophy was further indicated by heart weight to tibia length ratios. Significant changes in aortic samples also implicate an involvement of the vasculature. Chronic stress in humans and mice leads to an increase in inflammatory and pro-coagulant markers. In our study, inflammatory markers (LCN, IL-6, IL-17c, PTGS2) were shown to be significantly increased immediately after the period of chronic stress, however the markers return to non-significant levels when mice were allowed a recovery period. Chronic mental stress has a lasting and direct deleterious effect on the cardiovascular system and it is essential to understand these implications in an aging population.