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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1505.)
© 2008 American Heart Association, Inc.

Cell Biology/Signaling

Myocardin Is Sufficient for a Smooth Muscle-Like Contractile Phenotype

Xiaochun Long; Robert D. Bell; William T. Gerthoffer; Berislav V. Zlokovic; Joseph M. Miano

From the Aab Cardiovascular Research Institute (X.L., J.M.M.) and the Center for Neurodegenerative and Vascular Brain Disorders (R.D.B., B.V.Z.), University of Rochester School of Medicine & Dentistry, NY; and the University of South Alabama College of Medicine (W.T.G.), Mobile.

Correspondence to Joseph M. Miano, PhD, Aab Cardiovascular Research Institute, University of Rochester School of Medicine & Dentistry, 211 Bailey Road, Rochester, New York 14586. E-mail j.m.miano{at}rochester.edu

Background— Myocardin (Myocd) is a strong coactivator that binds the serum response factor (SRF) transcription factor over CArG elements embedded within smooth muscle cell (SMC) and cardiac muscle cyto-contractile genes. Here, we sought to ascertain whether Myocd-mediated gene expression confers a structural and physiological cardiac or SMC phenotype.

Methods and Results— Adenoviral-mediated expression of Myocd in the BC₃H1 cell line induces cardiac and SMC genes while suppressing both skeletal muscle markers and cell growth. Immunofluorescence microscopy shows that SRF and a SMC-like cyto-contractile apparatus are elevated with Myocd overexpression. A short hairpin RNA to Srf impairs BC₃H1 cyto-architecture; however, cotransduction with Myocd results in complete restoration of the cyto-architecture. Electron microscopic studies demonstrate a SMC ultrastructural phenotype with no evidence for cardiac sarcomerogenesis. Biochemical and time-lapsed videomicroscopy assays reveal clear evidence for Myocd-induced SMC-like contraction.

Conclusion— Myocd is sufficient for the establishment of a SMC-like contractile phenotype.

Though Myocd activates cardiac and smooth muscle genes, which cell type is conferred physiologically is unclear. We show Myocd overexpression is sufficient for structural and functional attributes of the smooth muscle contractile phenotype. Such studies have implications for understanding and treating a variety of smooth muscle-associated diseases where the normal contractile phenotype is destabilized.

Key Words: smooth muscle • serum response factor • myocardin • contraction • knockdown

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