title: Vascular smooth muscle cell phenotypic plasticity: focus on chromatin remodelling.
abstract: Differentiated vascular smooth muscle cells (SMCs) retain the capacity to modify their phenotype in response to inflammation or injury. This phenotypic switching is a crucial component of vascular disease, and is partly dependent on epigenetic regulation. An appreciation has been building in the literature for the essential role chromatin remodelling plays both in SMC lineage determination and in influencing changes in SMC behaviour and state. This process includes numerous chromatin regulatory elements and pathways such as histone acetyltransferases, deacetylases, and methyltransferases and other factors that act at SMC-specific marker sites to silence or permit access to the cellular transcriptional machinery and on other key regulatory elements such as myocardin and Kruppel-like factor 4 (KLF4). Various stimuli known to alter the SMC phenotype, such as transforming growth factor beta (TGF-β), platelet-derived growth factor (PDGF), oxidized phospholipids, and retinoic acid, appear to act in part through effects upon SMC chromatin structure. In recent years, specific covalent histone modifications that appear to establish SMC determinacy have been identified, while others alter the differentiation state. In this article, we review the mechanisms of chromatin remodelling as it applies to the SMC phenotype.
authors.affiliation: Department of Medicine, Division of Cardiology,  Stanford University School of Medicine, 300 Pasteur Drive, Falk CVRC, Stanford, CA 94305,  USA.
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Spin
authors.forename: Lars
authors.initials: L
authors.lastname: Maegdefessel
authors.forename: Philip S
authors.initials: PS
authors.lastname: Tsao
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D006801:Humans; D000090062:Kruppel-Like Factor 4; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism*; D010641:Phenotype
chemical_list: D002843:Chromatin; D006657:Histones; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4