MicroRNA-150 Protects the Heart From Injury by Inhibiting Monocyte Accumulation in a Mouse Model of Acute Myocardial Infarction. (February 2015)

• Record Type: Journal Article
• Authors: Liu, Zheng; Ye, Ping; Wang, Sihua; Wu, Jie; Sun, Yuan; Zhang, Anchen; Ren, Linyun; Cheng, Chao; Huang, Xiaofan; Wang, Ke; Deng, Peng; Wu, Chuangyan; Yue, Zhang; Xia, Jiahong
• Is Part Of: Circulation. Volume 8:Number 1(2015)
• Publication Date: 2015-02
• Subjects: Arrhythmia -- Periodicals; Heart -- Electric properties -- Periodicals; 616.1042
• DOI: 10.1161/CIRCGENETICS.114.000598
• Languages: English
• ISSNs: 1942-325X

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Background—</title> <p>MicroRNAs (miRs) and inflammatory monocytes participate in many cardiac pathophysiological processes including acute myocardial infarction (AMI). Recently, we observed that miR-150 is downregulated in injured mouse plasma after AMI as well as in human infarcted monocytes. However, the precise functional role of miR-150 in response to AMI remains unknown.</p> </sec> <sec> <title>Methods and Results—</title> <p>In a mouse model of AMI and in human subjects with AMI, we found that miR-150 expression was reduced in monocytes. In vitro studies showed that ectopic expression of miR-150 markedly reduced monocyte migration and proinflammatory cytokine production, whereas blockade of miR-150 had opposing effects. In vivo studies showed that overexpression of miR-150 in mice resulted in improved cardiac function, reduced myocardial infarction size, inhibition of apoptosis, and reduced inflammatory Ly-6C<sup>high</sup> monocyte invasion levels after AMI. Wild-type mice transplanted with miR-150 null (−/−) bone marrow cells could reverse this protective effect. Mechanistic studies demonstrated that miR-150 inhibited the expression of chemokine receptor 4 (CXCR4), thereby promoting monocyte migration.</p> </sec> <sec> <title>Conclusions—</title> <p>Our findings indicate that miR-150 acts as a critical regulator of monocyte cell migration and production of proinflammatory cytokines, leading to cardioprotective effects against AMI-induced injury. Thus, miR-150 may be a suitable target for therapeutic intervention in the setting of ischemic heart disease.</p> </sec> </abstract>