Adiponectin and its receptors are involved in hypertensive vascular injury

Abstract

Adipocyte-derived adiponectin (APN) is involved in the protection against cardiovascular disease, but the endogenous APN and its receptor expression in the perivascular adipocytes and their role in hypertensive vascular injury remain unclear. The present study aimed to detect endogenous APN and its receptor expression and their protective effects against hypertensive vascular injury. APN was mainly expressed in the perivascular adipocytes, while its receptors AdipoR1 and AdipoR2 were ubiquitously expressed in the blood vessels. Angiotensin II (Ang II)-induced hypertension resulted in a significant decrease of APN and AdipoR1 and AdipoR2 in the perivascular adipocytes and vascular cells. The migration assay used demonstrated that APN attenuated Ang II-induced vascular smooth muscle cells migration and p38 phosphorylation Furthermore, the in vivo study demonstrated that APN receptor agonist AdipoRon attenuated Ang II-induced hypertensive vascular hypertrophy and fibrosis. Taken together, the present study indicated that perivascular adipocytes-derived APN attenuated hypertensive vascular injury possibly via its receptor-mediated inhibition of p38 signaling pathway. obesity (5-7). However, APN attenuates cardiac inflammation and remodeling in the classical angiotensin II (Ang II)-induced hypertension model (8). However, the potential protective role of APN on the Ang II-induced vascular remodeling has not been fully elucidated. Adiponectin, as a fat-derived hormone, fulfills a critical role as an important messenger between adipocytes and other organs through the adiponectin receptor 1 and/or receptor 2 (AdipoR1/R2). These receptors are ubiquitously expressed in the adipose tissue, skeletal muscle and cardiovascular system (9,10). Previous studies have demonstrated that APN attenuates vascular remodeling through inhibiting vascular smooth muscle cell (VSMC) proliferation and phenotype trans differentiation (11,12). However, little is known about the endogenous APN and its receptor expression and function in the vasculatures of the Ang II-induced hypertensive model. In the present study, APN and AdipoR expression in vascular cells was demonstrated and the effects of APN on VSMCs migration were investigated. The distribution of these molecules in the vasculature of Ang-II induced hypertension were detected in vivo, and whether the APN receptor agonist AdipoRon could attenuate hypertension-associated vascular injury was determined.