Myocardin

There is a general consensus that perturbations to the vessel wall provoke a population of mature vascular smooth muscle cells (VSMCs) to either dedifferentiate into proliferating/migrating cells or transdifferentiate into new cell types.1 Such phenotypic plasticity has stimulated much research on the signaling pathways and transcriptional mediators, coordinating the expression of a growing number of genes (both coding and noncoding) that constitute a unique transcriptome for the differentiated state of VSMCs. The majority of such genes harbor 1 or more 10-bp codes known as CArG boxes to which the serum response factor (SRF) binds.2 More than 60 proteins interact with SRF to drive cofactor-dependent programs of gene expression. One prominent SRF cofactor is myocardin (MYOCD), which was first described as a cardiac muscle–enriched transcription factor that powerfully stimulates CArG-dependent promoters driving expression of cardiac-specific genes and contributes to normal cardiac muscle gene expression in vivo.3 Soon after its discovery in 2001, MYOCD was shown to similarly enhance activity of VSMC-restricted promoters in a CArG-dependent manner and induce expression of several of the corresponding endogenous transcripts in a cell line that does not express VSMC-restricted genes. Furthermore, Myocd mRNA was discovered to be abundantly expressed in aortic SMC, only to be reduced when such cells are placed in culture, suggesting MYOCD is important in maintaining the normal VSMC contractile phenotype.4 Subsequent studies confirmed and extended many of these findings, thus validating the role of MYOCD as a key component …