THE EFFECTS OF STRESS-INDUCED VIRAL REACTIVATION ON THE SR-BI PATHWAY AND ATHEROSCLEROSIS PATHOPHYSIOLOGY

Abstract

Chronic stress has become an issue that plagues modern day humanity. In short bursts, stress can be beneficial; however, in the longer term, stress can become harmful to the human body. Chronic stress leads to the overstimulation of the Hypothalamic-Pituitary-Adrenal Axis (HPA), resulting in an overproduction of cortisol. Initially this can aid in several anti-inflammatory responses, such as tissue repair; however, prolonged elevated cortisol levels may suppress the immune system and impair its ability to control opportunistic pathogens in the human body (Gu, et al., 2012). Previous studies in our lab have identified significant changes in the brain and heart of mice subjected to stressful environments and infection with murid herpes virus type 4. These findings suggest that there is a common factor causing this, which we believed could be vascular changes triggered by the stress response and the re-activation of latent viruses. The main objective of this study was to evaluate the impact of chronic stress-induced viral re-activation on the development of atherosclerosis through the suppression of the SR-BI/HDL pathway. SR-BI is a multi-functional scavenger receptor with high affinity for HDL that plays a role in lipid transport out of cells for loading onto HDL and delivery back to the liver for secretion (Linton, et al., 2017). It is expressed on macrophage and endothelial cells, which are key players in the pathogenesis of Atherosclerosis. In literature, it has been observed that in the absence of SR-BI, plaque formation occurs at a higher rate within arterial walls (van Eck, et al., 2003). According to the CDC, there currently exists a high prevalence of heart disease and stroke within underserved communities. These communities face increased levels of poverty that can directly translate into chronic stress within individuals. If this is paired with the re-activation of dormant viruses within individuals in these communities, then it may play a role in atherosclerosis induced vascular dysfunction that could explain the increased prevalence of heart disease and strokes. This study consisted of an in-vivo and in-vitro model in which mice and cells were studied to assess changes in gene and protein expression of atherogenic markers in response to chronic stress and viral infection. The in-vivo portion consisted of mice subjected to stress and infected with murid herpes virus 4 as a model of Epstein Barr virus infection in humans. The in-vitro portion of this study dealt with creating a model that could mimic stress and viral infection within cultured macrophage and endothelial cells with the use of Cortisol and Polyinosinic:polycytidylic acid (Poly I:C). The in-vivo and in-vitro studies were performed in tandem to reinforce the validity of the in-vivo results as well as to further isolate whether macrophages or endothelial cells within the brain and heart could contribute more to atherosclerosis development. Our results suggest that stress-induced viral re-activation may indeed play a significant role in the development of plaque within arteries and contribute to an increased risk of cardiovascular/neurovascular diseases.