Stargazing microRNA maps a new miR-21 star for cardiac hypertrophy

Abstract

Left ventricular hypertrophy is an initial compensatory mechanism in response to cardiac stress that can degenerate into heart failure and sudden cardiac death. Recent studies have shown that microRNAs (miRs) regulate several aspects of cardiovascular diseases. In this issue of the JCI, Bang and colleagues identified an exosome-mediated communication mechanism between cardiac fibroblasts and cardiomyocytes. Specifically, cardiac fibroblasts secrete miR-enriched exosomes, which are subsequently taken up by cardiomyocytes, in which they alter gene expression. In particular, a passenger strand miR, miR-21*, was identified as a potent paracrine factor that induces cardiomyocyte hypertrophy when shuttled through exosomes. These advanced comprehensive analyses represent a major step forward in our understanding of cardiovascular physiopathology, providing a promising adjunctive target for possible therapeutic approaches, namely the miR-mediated paracrine signaling network.

Figure 1. Dynamics of fibroblast-mediated exosome secretion and pivotal miRs involved in cardiac hypertrophy.

Following cardiac stress, fibroblasts secrete miR-enriched exosomes, which are enriched with miR-21*. Cardiomyocytes take up the fibroblast-secreted exosomes, which release miR-21*. Targeted knockdown of SORBS2 and PDLIM5 by miR-21* promotes hypertrophy. Many miRs that regulate hypertrophy have been identified and can be considered as tissue specific, circulating, and secreted. Among the latter, only miR-21* has been detected in pericardial fluid in the context of cardiac hypertrophy (21).