The role of endothelial and macrophage mineralocorticoid receptor in inflammation response and anti-contractile function of perivascular adipose tissue in obese male and female

Abstract

Obesity prevalence is increasing worldwide and is higher in women than men. High body mass index is a risk factor for cardiovascular diseases (CVD), and an impaired perivascular adipose tissue (PVAT) anticontractile function associated with PVAT inflammation have been demonstrated in obesity. Mineralocorticoid receptor (MR) is expressed in immune and endothelial cells (EC) and its activation could play a key role in the adipose tissue inflammation in obesity by inducing leucocytes adhesion and migration and modulate the inflammatory macrophage M1 and/or anti-inflammatory and residents M2 profile. MR blockade improves endothelial function and has anti-inflammatory effect in female obesity, but not in males. Therefore, MR raises as a potential mechanism involved in sex differences in the physiopathology of CVD in obesity. It still not known if MR participates in PVAT dysfunction in male and female obesity. We hypothesized that MR activation is involved in the inflammatory response in PVAT and contribute to obesity-induced vascular dysfunction. Male and female mice will be fed a chow or a high-fat diet and treated with the MR antagonist spironolactone. In addition, mice lacking MR in EC (EC-MR-/-) or in myeloid cells (MO-MR-/-) fed chow or a high-fat diet will be used to evaluate cell-specific role of MR activation in obesity. Mesenteric resistance arteries (<300¼m) and respective PVAT will be harvested. PVAT leucocyte infiltration, anti- and pro-inflammatory cytokines, macrophage polarization profile and oxidative stress will be evaluated. Mesenteric arteries will be used to evaluate vascular reactivity in the presence and absence PVAT.