Abstract 9742: Counteractive Effects of Omentin-1 Against Atherogenesis

Abstract

Introduction: Omentin-1, a novel adipocytokine expressed in visceral fat tissue, is negatively correlated with obesity, insulin resistance, and stable coronary artery disease (CAD). However, there have been no previous reports regarding the effects of omentin-1 on atherogenesis. Objective and Methods: We aimed to evaluate the atheroprotective effects of omentin-1 on human monocyte-derived macrophages, human aortic smooth muscle cells (HASMCs) in vitro , and aortic lesions in apolipoprotein E-deficient (ApoE -/- ) mice in vivo . The histological expression of omentin-1 in coronary artery lesions and epicardial adipose tissues and its plasma levels were compared between CAD and non-CAD patients. Results: Omentin-1 was abundantly expressed in human umbilical vein endothelial cells, macrophages, HASMCs, and human coronary artery SMCs in vitro . Omentin-1 promoted antiinflammatory M2 phenotype via PPAR-γ upregulation and NF-κB downregulation during differentiation of human monocytes into macrophages. Omentin-1 suppressed oxidized LDL-induced foam cell formation associated with downregulation of CD36, scavenger receptor class A, and acyl-CoA:cholesterol acyltransferase-1 and upregulation of neutral cholesterol ester hydrolase in human macrophages. In HASMCs, omentin-1 suppressed angiotensin II-induced migration and PDGF-BB-induced proliferation, and collagen-1 and collagen-3 expressions via ERK1/2 and NF-κB downregulation. Four-week infusion of omentin-1 into ApoE -/- mice retarded the development of aortic atherosclerotic lesions with reduced contents of monocytes/macrophages, SMCs, and collagen fibers. In addition, it increased peritoneal M2-activated macrophages, downregulated inflammasomes such as CRP, NF-κB, COX-2, and apoptosis-associated speck-like protein containing a caspase recruitment domain, and lowered plasma total cholesterol levels in ApoE -/- mice. Omentin-1 levels were markedly reduced in coronary endothelium and epicardial fat but increased in plasma and atheromatous plaques (macrophages/SMCs) in CAD patients compared with non-CAD patients. Conclusions: Our translational research provided the first evidence that omentin-1 may serve as a novel therapeutic target for atherosclerosis and CAD.