Emory Specialized Center of Research Excellence (SCORE) on Sex Differences

Emory University, Atlanta GA

Investigators

Linked publications, trials & patents

Abstract

PROJECT SUMMARY / ABSTRACT (Project 3: Heart) Persistent inflammation and immune dysregulation play a pivotal role in the early onset of cardiovascular disease (CVD) in HIV. Among women living with HIV (WLH), CVD risk is further compounded by estrogen deficiency and early menopause that have a significant impact on the gut, by inducing dysbiosis from disruption of the gut integrity, leading to microbial translocation and systemic inflammation that in turn promotes vascular disease and its progression. In the Emory SCORE tripartite Bone, Brain, Heart (BBH) study, both WLH and women at risk for HIV (WRH) had a significantly higher burden of both traditional CVD risk factors and psycho-social risk factors compared to an independent control population of age- and sex-matched women, recruited from the same geographical area into the Center for Health Discovery and Wellbeing (CHDWB). They also had a greater than expected prevalence of sub-clinical CVD measured as endothelial dysfunction and coronary atherosclerosis that were measured using coronary CT angiography and calcification. We also found that circulating progenitor cell (CPC) levels, a measure of endogenous regenerative capacity, were higher in WLH compared CHDWB controls, demonstrating stimulation of bone marrow regenerative activity by HIV. However, lower CPC counts were associated with the presence of coronary atherosclerosis in WLH. Because these cross-sectional relationships suggest, but do not confirm, causal links between potential mechanisms including (i) gut barrier impairment/dysbiosis-mediated inflammation to premature CVD in WLH, (ii) changes in regenerative capacity, and (iii) psycho-social stress risk factor burden, in our renewal application, we propose to investigate whether progression of sub-clinical CVD over a 5-year period is greater in WLH. We will leverage the already recruited age- and race-matched population from CHDWB as controls. We will explore whether such progression is moderated by a) HIV and/or estrogen deficiency induced gut disruption and the associated immune dysregulation (Aim 1), b) reduced endogenous regenerative capacity (Aim 2), and c) psycho-social factors (Aim 3). Because CVD is higher in WLH and also in women following menopausal transition, our overarching goal is to investigate the extent to which HIV and/or estrogen deficiency impact on the gut co-act to mediate the factors driving the high burden of CVD in WLH especially during the period of menopausal transition.