Pro-Inflammatory Adipokines and the Perivascular Adipose Tissue Phenotype in Females Ovariectomized SHR: Influence of Estrogen

Abstract

The vasoprotective effect of estrogen on the cardiovascular system of pre-and postmenopausal women remains not understood. The reduction of estrogen levels during postmenopausal women is a risk factor for cardiovascular and metabolic diseases. However, the mechanisms of estrogen impact vascular function are not yet fully understood. Several studies suggested that estrogen, by nuclear estrogen receptors, contributes to inflammatory and redox balance in vasculature. Endothelial cells from postmenopausal women present a more pronounced proinflammatory profile than those from premenopausal women, suggesting a hormone effect in this conduction. Another crucial component in the modulation of vascular tonus is the perivascular adipose tissue (PVAT), which secretes vasoactive mediators inducing an anticontractile effect on vasculature. However, the impact of the absence of estrogen on PVAT has still not been explored.Estrogen has a direct effect on visceral adipose tissue, regulating adipogenesis. Taken together, the lack of estrogen leads to endothelial dysfunction; it is plausible that estrogen also modulates the function and phenotype of PVAT. Recently, we demonstrated that, in a normotensive model genetically modified to overexpression of estrogen receptor alpha in adipose tissue, the classical anticontractile effect of PVAT was intensified. We hypothesize that the PVAT of ovariectomized spontaneously hypertensive females (SHR) presents an exacerbated proinflammatory profile, inducing a change in the phenotype of the tissue, compared to control females, and that estrogen restores this condition. The project aims to identify which adipokines are regulated by estrogen and how they act on the PVAT phenotype. Thus, new potential therapeutic targets and biomarkers for understanding cardiovascular diseases in postmenopausal women may be specific.