Chemerin stimulates aortic smooth muscle cell proliferation and migration via activation of autophagy in VSMCs of metabolic hypertension rats.

Vascular remodeling is a characteristic pathogenesis of hypertension and a main cause of abnormal construction and function of organs because of hypertension. Chemerin is a new adipokine that is elevated in states of obesity and metabolic syndrome (MS). However, the molecular mechanisms behind these pathological processes are not fully clarified. An animal model of metabolic hypertension was created to evaluate the role of metabolic chemerin in hypertension. In this study, the expression of chemerin/CMKLR-1 and autophagy in the arteries of metabolic hypertension rats undergoing vascular remodeling was investigated and the effect and mechanisms on the regulation of human aortic smooth muscle cells (HA-SMCs) were explored. The vascular remodeling in vivo was more serious in the metabolic hypertensive rat model, and the expression of chemerin and its receptor CMKLR1 were remarkably higher in the media layer of the thoracic aorta and the mesenteric artery in metabolic hypertension rats. In addition, there was an increased number of autophagosomes in SMCs and an up-regulation of the autophagy-related protein LC3 and beclin-1 levels in metabolic hypertension rats. In vitro, chemerin significantly stimulated HA-SMC proliferation and migration, as determined by MTT assay and scratch assay, respectively. Chemerin significantly increased LC3 and beclin-1 levels, as measured by western blot analysis, while this effect was inhibited by the autophagy inhibitor 3-MA. It is demonstrated that chemerin stimulates SMC proliferation and migration via autophagy, which may lead to vascular structural remodeling in metabolic hypertension.