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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1416.)
© 2008 American Heart Association, Inc.

Editorials

Myocardin

Dominant Driver of the Smooth Muscle Cell Contractile Phenotype

Michael S. Parmacek

From the University of Pennsylvania Cardiovascular Institute, Philadelphia.

Correspondence to Michael S. Parmacek, MD, Division of Cardiovascular Medicine, Department of Medicine, University of Pennsylvania School of Medicine, 9035 Gates Pavilion, 3400 Spruce St., Philadelphia, PA 19104. E-mail Michael.parmacek@uphs.upenn.edu

An extract of the first 250 words of the full text is provided, because this article has no 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 see^1,2). 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 SM22, SM-MyHC, and SM--actin.⁷ In response to vascular injury, extrinsic cues and intracellular signals converge on myocardin/SRF complexes ultimately regulating and modulating vascular SMC phenotype (for review see^9,10). Mice harboring a null mutation in the myocardin gene survive only to embryonic day (E)10.5 and exhibit obvious defects in the embryonic and extraembryonic vasculature . . . [Full Text of this Article]

Related Article:

Myocardin Is Sufficient for a Smooth Muscle-Like Contractile Phenotype

Xiaochun Long, Robert D. Bell, William T. Gerthoffer, Berislav V. Zlokovic, and Joseph M. Miano
Arterioscler Thromb Vasc Biol 2008 28: 1505-1510. [Abstract] [Full Text] [PDF]