Myocardin

Abstract

A distinguishing feature of the smooth muscle cell (SMC) lineage is its remarkable plasticity required for maintenance and adaptation of the cardiovascular system. The biological properties of SMCs are ultimately determined by the orchestrated expression of genes encoding contractile and cytoskeletal proteins, intracellular enzymes, and cell surface ligands and receptors (for review see1,2⇓). In the postnatal vasculature, medial SMCs exit the cell cycle and assume a “contractile” phenotype required for regulation of vascular tone.3,4⇓ However, in response to vascular injury, SMCs reenter the cell cycle, downregulate expression of contractile proteins, and assume a “synthetic” phenotype resembling a fibroblast.3,4⇓ The modulation of vascular SMC phenotype has been implicated in the pathogenesis of vascular proliferative syndromes including atherosclerosis, restenosis, pulmonary hypertension, and transplant arteriopathy (for review see5). See accompanying article on page 1505 Myocardin ( Myocd ) is a recently discovered SMC-restricted transcriptional coactivator that physically associates with the MADS box transcription factor, SRF, to synergistically activate transcription of genes encoding SMC-restricted cytoskeletal and contractile proteins.6 Forced expression of myocardin transactivates multiple SMC-restricted transcriptional regulatory elements.6–8⇓⇓ Remarkably, forced expression of myocardin in embryonic stem (ES) cells induces expression of multiple endogenous SMC genes including SM22α, SM-MyHC, and SM-α-actin.7 In response to vascular …