AUTHOR=Lin Xuze , Sun Yan , Yang Shiwei , Yu Mengyue , Pan Liu , Yang Jie , Yang Jiaqi , Shao Qiaoyu , Liu Jinxing , Liu Yan , Zhou Yujie , Wang Zhijian 

TITLE=Omentin-1 Modulates Macrophage Function via Integrin Receptors αvβ3 and αvβ5 and Reverses Plaque Vulnerability in Animal Models of Atherosclerosis

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 8 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2021.757926

DOI=10.3389/fcvm.2021.757926

ISSN=2297-055X

ABSTRACT=Backgrounds: Omentin-1 is a novel cytokine which is primarily released by epicardial adipose tissue. Molecular structure analysis revealed that it contained a fibrinogen-like domain. Clinical studies have demonstrated that the expression of omentin-1 is tightly associated with the development of cardiovascular diseases, but the receptor by which omentin-1 modulates macrophage function has not been identified yet.
Objective: This study was sought to investigate the effect of omentin-1 on already-established atherosclerosis (AS) lesion in both ApoE-/- and Ldlr-/- mouse. And further study its underlying mechanisms.
Methods and results: We investigated the effect of omentin-1 on the plaque phenotype by implanting minipump in ApoE-/- and Ldlr-/- mouse. In vivo studies showed that the infusion of omentin-1 increased the collagen content and mitigated the formation of necrotic core in both animal models. Immunohistochemistry and immunofluorescence analysis revealed that omentin-1 suppressed inflammatory cytokines expression, macrophage infiltration and apoptosis within the plaque. Immunoprecipitation experiment and confocal microscopy analysis confirmed the binding of omentin-1 to integrin receptor αvβ3 and αvβ5. Cell studies demonstrated that omentin-1 suppressed the apoptosis and inflammatory cytokines expression induced by oxidized low-density lipoprotein in macrophage. In addition, omentin-1 promoted the phosphorylation of integrin-relevant signaling pathway as well as Akt and AMPK in macrophage. The adding of the inhibitor of integrin receptor or interfering the expression of integrin subunit αv (ITGAV) both significantly abrogated the bioeffects induced by omentin-1. Flowcytometry analysis indicated that antibodies against αvβ3 and αvβ5 had a competitive effect on omentin-1 binding to cell membrane.
Conclusions: The administration of adipokine omentin-1 can inhibit the necrotic cores formation and pro-inflammatory cytokines expression within the AS lesion. The mechanisms may include the suppression of apoptosis and pro-inflammatory cytokines expression in macrophage by binding to integrin receptor αvβ3 and αvβ5.