In Search of Novel Targets for Heart Disease: Myocardin and Myocardin-Related Transcriptional Cofactors

Figure 2

Dissecting the cell-autonomous roles of myocardin and MRTF-A in adult ventricular myocardium. Red arrows indicate up- or downregulation. In cardiomyocytes, forced expression of either Myocd or Mrtf-A induces hypertrophic gene expression and myocyte enlargement, whereas inhibition of any of these factors markedly attenuates hypertrophic responses. Although both factors display prohypertrophic activities, MYOCD, but not MRTF-A, is absolutely required for myocyte structural integrity and survival [43]. In cardiac fibroblasts, forced expression of Mrtf-A activates profibrosis gene expression and myofibroblast differentiation, whereas a loss of functional Mrtf-A leads to opposite effects. Forced Myocd expression stimulates both SM (including markers of myofibroblast differentiation) and cardiac genes (including cardiac ion channels and connexins) in ventricular fibroblasts.