Interleukin 33 contribution in vascular changes mediated by perivascular adipose tissue in mice submitted to high-fat diet

Abstract

Obesity triggers structural and functional changes in the perivascular adipose tissue (PVAT), leading to an imbalance in the production and release of PVAT-derived factors, in favor of vasoconstrictor and pro-inflammatory factors, as well as to changes in signaling pathways activated by these factors in vascular cells. An important mechanism proposed to explain the loss of the anti-contractile effects of PVAT in obesity involves inflammatory mediators. Recent studies show that interleukin 33 (IL-33) via activation of its receptor (ST2 receptor) is essential for the development and maintenance of regulatory T cells (Tregs) in the visceral adipose tissue. Tregs function is compromised in obesity, but the mechanisms involved are unknown. This study will test the hypothesis that increased energy consumption and obesity reduce the levels and function of IL-33, leading to decreased number and function of Tregs in the PVAT. To test our hypothesis, we will use Balb/C mice and knockout mice for the IL-33 receptor (ST2 receptor), and perform vascular reactivity and cellular and molecular analyses.