Plasma levels of chemerin， an adipocytokine produced from the adipose tissues and liver， are associated with metabolic syndrome and coronary artery disease (CAD). Chemerin and its analog， chemerin-9， are known to bind to their receptor， ChemR23. However， whether chemerin and chemerin-9 affect atherogenesis remains to be elucidated. We investigated the expression of chemerin and ChemR23 in human coronary arteries and cultured human vascular cells. The effects of chemerin and chemerin-9 on atheroprone phenomena were assessed in human THP1 monocytes， human umbilical vein endothelial cells (HUVECs)， and human aortic smooth muscle cells (HASMCs) and aortic lesions in mice. In patients with CAD， a ... More
Plasma levels of chemerin， an adipocytokine produced from the adipose tissues and liver， are associated with metabolic syndrome and coronary artery disease (CAD). Chemerin and its analog， chemerin-9， are known to bind to their receptor， ChemR23. However， whether chemerin and chemerin-9 affect atherogenesis remains to be elucidated. We investigated the expression of chemerin and ChemR23 in human coronary arteries and cultured human vascular cells. The effects of chemerin and chemerin-9 on atheroprone phenomena were assessed in human THP1 monocytes， human umbilical vein endothelial cells (HUVECs)， and human aortic smooth muscle cells (HASMCs) and aortic lesions in mice. In patients with CAD， a small amount of ChemR23， but not chemerin， was expressed within atheromatous plaques in coronary arteries. Chemerin and ChemR23 were expressed at high levels in THP1 monocytes， THP1-derived macrophages， and HUVECs; however， their expression in HASMCs was weak. Chemerin and chemerin-9 significantly suppressed the tumor necrosis factor-α (TNF-α)-induced mRNA expression of adhesion and pro-inflammatory molecules in HUVECs. Chemerin and chemerin-9 significantly attenuated the TNF-α-induced adhesion of THP1 monocytes to HUVECs and macrophage inflammatory phenotype. Chemerin and chemerin-9 suppressed oxidized low-density lipoprotein (oxLDL)-induced macrophage foam cell formation associated with down-regulation of CD36 and up-regulation of ATP-binding cassette transporter A1 (ABCA1). In HASMCs， chemerin and chemerin-9 significantly suppressed migration and proliferation without inducing apoptosis. In the mice， a 4-week infusion of chemerin-9 significantly decreased the areas of aortic atherosclerotic lesions by reducing intraplaque macrophage and SMC contents. Our results indicate that chemerin-9 prevents atherosclerosis. Therefore， the development of chemerin analogs/ChemR23 agonists may serve as a novel therapeutic target for atherosclerotic diseases.
