title: Vascular smooth muscle cell phenotypic plasticity and the regulation of vascular calcification.
abstract: Vascular smooth muscle cells (VSMCs) exhibit an extraordinary capacity to undergo phenotypic change during development, in vitro and in association with disease. Unlike other muscle cells they do not terminally differentiate. Development and maintenance of the mature contractile phenotype is regulated by a number of interacting transcription factors. In response to injury contractile VSMCs can be induced to change phenotype, proliferate and migrate to effect repair. On completion of the repair process VSMCs return to a nonproliferating contractile phenotype. In this way, in the context of atherosclerosis, a protective fibrous cap is formed and maintained at sites of injury. However in disease, when modulatory signals are perturbed, this phenotypic transition is dysregulated and VSMCs are induced to undergo inappropriate differentiation into cells with features of other mesenchymal lineages such as osteoblasts, chondrocytes and adipocytes. Moreover, evidence is accumulating that these aberrant phenotypic transitions contribute to the pathogenesis of vascular diseases such as atherosclerosis and Monckeberg's Sclerosis. Indeed, the osteo/chondrocytic conversion of VSMCs and the association of this phenotype with vascular calcification is a paradigm for how inappropriate differentiation can influence disease processes. Understanding of the mechanisms and signalling pathways involved in this particular phenotype change is well advanced offering the possibility for the design of successful therapeutic interventions in the future.
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK.
authors.forename: V P
authors.initials: VP
authors.lastname: Iyemere
authors.forename: D
authors.initials: D
authors.lastname: Proudfoot
authors.forename: P L
authors.initials: PL
authors.lastname: Weissberg
authors.forename: C M
authors.initials: CM
authors.lastname: Shanahan
mesh_terms: D002114:Calcinosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D003460:Crystallization; D016207:Cytokines / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D015398:Signal Transduction; D014652:Vascular Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology*
chemical_list: D016207:Cytokines; D006133:Growth Substances; D002118:Calcium