This Article Free upon publication Full Text Full Text (PDF) Data Supplement All Versions of this Article: 28/8/1505    most recent ATVBAHA.108.166066v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Google Scholar Articles by Long, X. Articles by Miano, J. M. PubMed PubMed Citation Articles by Long, X. Articles by Miano, J. M. Related Collections Related Article

(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

Abstract

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

Related Article:

Myocardin: Dominant Driver of the Smooth Muscle Cell Contractile Phenotype

Michael S. Parmacek
Arterioscler. Thromb. Vasc. Biol. 2008 28: 1416-1417. [Full Text] [PDF]

This article has been cited by other articles:

				M. S. Parmacek Myocardin: Dominant Driver of the Smooth Muscle Cell Contractile Phenotype Arterioscler. Thromb. Vasc. Biol., August 1, 2008; 28(8): 1416 - 1417. [Full Text] [PDF]