Chemerin-9, a potent agonist of chemerin receptor (ChemR23), prevents atherogenesis

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  Apoe -/- 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 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-induced macrophage foam cell formation associated with downregulation of CD36 and upregulation of ATP-binding cassette transporter A1. In HASMCs, chemerin and chemer...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research