Abstract 136: Mineralocorticoid Receptor Activation In Macrophages Mediates High Fat/high Sucrose Induced Vascular Stiffness in Female Mice

Abstract

Enhanced mineralocorticoid receptor (MR) activation promotes vascular dysfunction and remodeling. We studied the role of MR activation in perivascular adipose tissue (PVAT) macrophages in the development of high-fat/high-fructose diet (“Western Diet”, WD) induced vascular stiffness in female mice. Myeloid MR KO mice (MyMRKO) were fed a WD for 8 weeks (n=3). MyMRKO female mice (n=2) were infused with aldosterone (Aldo) for 3 weeks. Aortic stiffness was assessed in vivo by pulse wave velocity and ex vivo by atomic force microscopy. Vascular reactivity was studied in aortic rings. MyMRKO mice were protected from Aldo and WD induced aortic stiffness and had greater endothelial-dependent and independent vasodilation compared to littermates (Fig. 1, 2). Immunohistochemistry suggested decreased peri-aortic fibrosis and macrophage infiltration in Aldo infused MyMRKO (Fig.1). We conclude that MR KO in myeloid cells protects against WD and Aldo-induced vascular stiffness in female mice. Our data support a role for MR activation in PVAT macrophages in the pathogenesis of WD-induced vascular dysfunction.