MicroRNA-155 in the Heart

Cardiovascular complications arising as a consequence of vascular disease are on the rise in the world, with an urgent need to develop therapies that can prevent the drivers of atherosclerosis and promote healing of infarcted tissue after an ischemic event. Rupture of culprit atherosclerotic lesions is the main driver of downstream myocardial infarction (MI), accounting for 7 million deaths annually and 23 million individuals living with heart failure worldwide.1 Accordingly, there has been a tremendous interest in using novel therapies to revascularize ischemic tissue and to repair damaged myocardium after MI.2 Although there is a clear clinical need to promote collateral vessel growth to facilitate healing and to preserve tissue integrity after an ischemic event, the mechanisms that govern the growth of collateral vessels remain largely unknown. In this issue of Circulation , Pankratz and colleagues3 use microRNAs (miRNAs) to study the different mechanisms that promote angiogenesis and arteriogenesis and find that microRNA-155 (miR-155) has dual and opposing roles in both processes.Article see p 1575The authors first set out to discover the miRNA-based mechanisms that promote neovascularization. Using a model of femoral artery ligation, they found the expression of 30 miRNAs differentially regulated 7 days after ligation. On the basis of the substantial downregulation of miR-155 during this neovascularization period, they hypothesized that miR-155 antagonizes factors that regulate angiogenesis. Indeed, they followed up by showing that endothelial cells (ECs) devoid of miR-155 (from miR-155−/− mice) have an improved angiogenic capacity compared with wild-type ECs and concluded that miR-155 antagonizes angiogenesis. They demonstrated that miR-155 was able to inhibit angiogenesis through inhibition of AGTR1, a known miR-155 target gene that promotes angiogenesis and inhibits inflammation, in ECs.4 Using an in vivo Matrigel assay that assesses the sprouting of new capillaries into a basement membrane-like …