Abstract 9701: A Novel Adipocytokine Chemerin Stimulates Proliferation and Hypercontractility of Vascular Smooth Muscle: Implication for Pathogenesis of Obesity-related Hypertension

Abstract

Chemerin is a recently identified adipose tissue-derived cytokine (adipocytokine) which plays roles in inflammatory responses of immune cells such as dendritic cells and macrophages as well as differentiation and metabolisms of adipocytes. Chemerin acts as a chemoattractant for the immune cells, while it induces differentiation of adipocytes and glucose tolerance. Blood chemerin level increases in patients with obesity, and correlates positively with several key factors of metabolic syndrome such as body mass index and triglyceride level. Since blood chemerin level also correlates positively with systolic blood pressure in the obese subjects, we hypothesized that chemerin might relate to pathogenesis of obesity-related hypertension. To test the hypothesis, we examined the effects of chemerin on proliferation and contractility of vascular smooth muscle which play key roles in the development of hypertension. In cultured rat mesenteric arterial smooth muscle cells (SMCs), chemerin (1-100 ng/ml, 24h) stimulated proliferation in a concentration-dependent manner (n=8, P<0.01). Chemerin (100 ng/ml, 20 min) stimulated phosphorylation of Akt (n=8, P<0.05), and an Akt inhibitor prevented the chemerin-induced SMCs proliferation (n=4). Chemerin produced oxidant radicals in SMCs, and an anti-oxidant drug, N-acetyl-L-cysteine inhibited SMCs proliferation (n=6) and Akt phosphorylation (n=4, P<0.05). In rat isolated mesenteric artery, chemerin (100 ng/ml, 30 min) augmented noradenaline (1 nM-1 μM)-induced concentration-dependent contraction (n=6, P<0.05). The effect was higher in endothelium-intact artery than endothelium-denuded artery (n=7), and was normalized by an endothelin type A receptor blocker, BQ123 (n=13). Chemerin had no influence on noradrenaline-stimulated endothelial nitric oxide production (n=10). The present results for the first time demonstrated that chemerin stimulates proliferation of vascular SMCs via oxidative-stress-dependent Akt activation. It is also demonstrated that chemerin mediates hypercontractility of isolated mesenteric artery likely via endothelial-derived endothelin-1. The results may represent chemerin as a new adipocytokine to understand the link between obesity and hypertension.