MicroRNA-150 protects the heart from injury by inhibiting monocyte accumulation in a mouse model of acute myocardial infarction.

Abstract

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. 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(high) 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. 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.