title: Counteractive effects of omentin-1 against atherogenesis†.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  This study was performed 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 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. Omentin-1 was abundantly expressed in human umbilical vein endothelial cells, macrophages, HASMCs, and human coronary artery SMCs in vitro. Omentin-1 promoted anti-inflammatory M2 phenotype during differentiation of human monocytes into macrophages. Omentin-1 suppressed oxidized low-density lipoprotein-induced foam cell formation associated with down-regulation of CD36, scavenger receptor class A, and acyl-CoA:cholesterol acyltransferase-1 and up-regulation of neutral cholesterol ester hydrolase in human macrophages. Omentin-1 suppressed angiotensin II-induced migration and platelet-derived growth factor-BB-induced proliferation, and collagen-1 and -3 expression in HASMCs. 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 fibres along with peritoneal M2-activated macrophages with inflammasome down-regulation and lowered plasma total cholesterol levels. 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
  This study provided the first evidence that omentin-1 may serve as a novel therapeutic target for atherosclerosis and CAD.
authors.affiliation: Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-City, Tokyo 192-0393, Japan.
authors.forename: Kaho
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-City, Tokyo 192-0393, Japan.
authors.forename: Rena
authors.initials: R
authors.lastname: Watanabe
authors.affiliation: Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-City, Tokyo 192-0393, Japan.
authors.forename: Hanae
authors.initials: H
authors.lastname: Konii
authors.affiliation: Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-City, Tokyo 192-0393, Japan.
authors.forename: Remina
authors.initials: R
authors.lastname: Shirai
authors.affiliation: Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-City, Tokyo 192-0393, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Pathology, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Taka-Aki
authors.initials: TA
authors.lastname: Matsuyama
authors.affiliation: Department of Pathology, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Hatsue
authors.initials: H
authors.lastname: Ishibashi-Ueda
authors.affiliation: Division of Cardiology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Koba
authors.affiliation: Division of Cardiology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Youichi
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hirano
authors.affiliation: Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-City, Tokyo 192-0393, Japan watanabe@toyaku.ac.jp.
authors.forename: Takuya
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000328:Adult; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000378:metabolism* / Q000628:therapy; D002465:Cell Movement / Q000502:physiology; D016207:Cytokines / Q000378:metabolism*; D015536:Down-Regulation; D005487:Foam Cells / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D009000:Monocytes / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D001057:Apolipoproteins E; D016207:Cytokines; D058851:GPI-Linked Proteins; C432397:ITLN1 protein, human; D037102:Lectins; D008077:Lipoproteins, LDL; D010982:Platelet-Derived Growth Factor; C099252:oxidized low density lipoprotein
keywords: Adipocytokine; Atherosclerosis; Coronary artery disease; Macrophage; Vascular smooth muscle cell