title: Vascular Smooth Muscle Cells in Atherosclerosis.
abstract: The historical view of vascular smooth muscle cells (VSMCs) in atherosclerosis is that aberrant proliferation of VSMCs promotes plaque formation, but that VSMCs in advanced plaques are entirely beneficial, for example preventing rupture of the fibrous cap. However, this view has been based on ideas that there is a homogenous population of VSMCs within the plaque, that can be identified separate from other plaque cells (particularly macrophages) using standard VSMC and macrophage immunohistochemical markers. More recent genetic lineage tracing studies have shown that VSMC phenotypic switching results in less-differentiated forms that lack VSMC markers including macrophage-like cells, and this switching directly promotes atherosclerosis. In addition, VSMC proliferation may be beneficial throughout atherogenesis, and not just in advanced lesions, whereas VSMC apoptosis, cell senescence, and VSMC-derived macrophage-like cells may promote inflammation. We review the effect of embryological origin on VSMC behavior in atherosclerosis, the role, regulation and consequences of phenotypic switching, the evidence for different origins of VSMCs, and the role of individual processes that VSMCs undergo in atherosclerosis in regard to plaque formation and the structure of advanced lesions. We think there is now compelling evidence that a full understanding of VSMC behavior in atherosclerosis is critical to identify therapeutic targets to both prevent and treat atherosclerosis.
authors.affiliation: From the Division of Cardiovascular Medicine, Addenbrooke's Centre for Clinical Investigation, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom (M.R.B., S.S.); and University of Virginia School of Medicine, Charlottesville (G.K.O.). mrb@mole.bio.cam.ac.uk.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Bennett
authors.affiliation: From the Division of Cardiovascular Medicine, Addenbrooke's Centre for Clinical Investigation, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom (M.R.B., S.S.); and University of Virginia School of Medicine, Charlottesville (G.K.O.).
authors.forename: Sanjay
authors.initials: S
authors.lastname: Sinha
authors.affiliation: From the Division of Cardiovascular Medicine, Addenbrooke's Centre for Clinical Investigation, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom (M.R.B., S.S.); and University of Virginia School of Medicine, Charlottesville (G.K.O.).
authors.forename: Gary K
authors.initials: GK
authors.lastname: Owens
mesh_terms: D000818:Animals; D017209:Apoptosis; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D016922:Cellular Senescence; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D015398:Signal Transduction
keywords: atherosclerosis; extracellular matrix; interleukin; platelet-derived growth factor; smooth muscle