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. 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. This study provided the first evidence that omentin-1 may serve as a novel therapeutic target for atherosclerosis and CAD.

Adropin, a peptide hormone expressed in liver and brain, is known to improve insulin resistance and endothelial dysfunction. Serum levels of adropin are negatively associated with the severity of coronary artery disease. However, it remains unknown whether adropin could modulate atherogenesis. We assessed the effects of adropin on inflammatory molecule expression and human THP1 monocyte adhesion in human umbilical vein endothelial cells (HUVECs), foam cell formation in THP1 monocyte-derived macrophages, and the migration and proliferation of human aortic smooth muscle cells (HASMCs) in vitro and atherogenesis in Apoe^−/− mice in vivo. Adropin was expressed in THP1 monocytes, their derived macrophages, HASMCs, and HUVECs. Adropin suppressed tumor necrosis factor α-induced THP1 monocyte adhesion to HUVECs, which was associated with vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 downregulation in HUVECs. Adropin shifted the phenotype to anti-inflammatory M2 rather than pro-inflammatory M1 via peroxisome proliferator-activated receptor γ upregulation during monocyte differentiation into macrophages. Adropin had no significant effects on oxidized low-density lipoprotein-induced foam cell formation in macrophages. In HASMCs, adropin suppressed the migration and proliferation without inducing apoptosis via ERK1/2 and Bax downregulation and phosphoinositide 3-kinase/Akt/Bcl2 upregulation. Chronic administration of adropin to Apoe^−/− mice attenuated the development of atherosclerotic lesions in the aorta, with reduced the intra-plaque monocyte/macrophage infiltration and smooth muscle cell content. Thus, adropin could serve as a novel therapeutic target in atherosclerosis and related diseases.

Catestatin, a catecholamine-release inhibitory peptide, has multiple cardiovascular activities. Conflicting results have been recently reported by increased or decreased plasma levels of catestatin in patients with coronary artery disease (CAD). However, there have been no previous reports regarding the effects of catestatin on arteriosclerosis. This study evaluated the vasoprotective effects of catestatin on human macrophages, human aortic smooth muscle cells (HASMCs) and human umbilical vein endothelial cells (HUVECs) in vitro, and aortic atherosclerosis and wire injury-induced femoral artery neointimal hyperplasia in apolipoprotein E–deficient (ApoE^−/−) mice fed with a high-cholesterol diet. Histological expression of catestatin in coronary artery lesions and its plasma level were compared between CAD and non-CAD patients. Catestatin was abundantly expressed in cultured human monocytes, macrophages, HASMCs and HUVECs. Catestatin significantly suppressed lipopolysaccharide-induced upregulation of tumour necrosis factor-α, vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in HUVECs. Catestatin significantly suppressed inflammatory responses and oxidized low-density lipoprotein-induced foam cell formation associated with acyl-CoA:cholesterol acyltransferase-1 downregulation and ATP-binding cassette transporter A1 upregulation in human macrophages. Catestatin significantly suppressed migration, proliferation and collagen-1 expression without inducing apoptosis, and increased elastin and fibronectin expression in HASMCs. Administration of catestatin into ApoE^−/− mice significantly retarded entire aortic atherosclerotic lesions with declined contents of macrophages, SMCs and collagen fibres in atheromatous plaques, but not the femoral artery injury–induced neointimal hyperplasia. In CAD patients, catestatin levels were significantly decreased in plasma but increased in coronary atheromatous plaques. This study provided the first evidence that catestatin could prevent macrophage-driven atherosclerosis, but not SMC-derived neointimal hyperplasia after vascular injury.