Abstract: HomeCirculation ResearchVol. 112, No. 1Smooth Muscle Cell Plasticity Free AccessReview ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessReview ArticlePDF/EPUBSmooth Muscle Cell PlasticityFact or Fiction? Anh T. Nguyen, Delphine Gomez, Robert D. Bell, Julie H. Campbell, Alexander W. Clowes, Giulio Gabbiani, Cecilia M. Giachelli, Michael S. Parmacek, Elaine W. Raines, Nancy J. Rusch, Mei Y. Speer, Michael Sturek, Johan Thyberg, Dwight A. Towler, Mary C. Weiser-Evans, Chen Yan, Joseph M. Miano and Gary K. Owens Anh T. NguyenAnh T. Nguyen From the University of Virginia, Cardiovascular Research Center, Charlottesville, VA (A.T.N., D.G.,G.K.O.); Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY (R.D.B., C.Y., J.M.M.); Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia (J.H.C.); Department of Surgery (A.W.C.) and Department of Pathology (E.W.R.), University of Washington School of Medicine, Seattle, WA; Department of Pathology and Immunology, Faculty of medicine, University of Geneva, Geneva, Switzerland (G.G.); Department of Bioengineering, University of Washington, Seattle, WA (C.M.G., M.Y.S.); Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.S.P.) Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR (N.J.R.); Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN (M.S.); Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (J.T.); Department of Medicine, Endocrine Division, Washington University, St. Louis, MO (D.A.T.); and Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado, Anshutz Medical Campus, Aurora, CO (M.C.W.-E.). Search for more papers by this author , Delphine GomezDelphine Gomez From the University of Virginia, Cardiovascular Research Center, Charlottesville, VA (A.T.N., D.G.,G.K.O.); Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY (R.D.B., C.Y., J.M.M.); Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia (J.H.C.); Department of Surgery (A.W.C.) and Department of Pathology (E.W.R.), University of Washington School of Medicine, Seattle, WA; Department of Pathology and Immunology, Faculty of medicine, University of Geneva, Geneva, Switzerland (G.G.); Department of Bioengineering, University of Washington, Seattle, WA (C.M.G., M.Y.S.); Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.S.P.) Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR (N.J.R.); Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN (M.S.); Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (J.T.); Department of Medicine, Endocrine Division, Washington University, St. Louis, MO (D.A.T.); and Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado, Anshutz Medical Campus, Aurora, CO (M.C.W.-E.). Search for more papers by this author , Robert D. BellRobert D. Bell From the University of Virginia, Cardiovascular Research Center, Charlottesville, VA (A.T.N., D.G.,G.K.O.); Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY (R.D.B., C.Y., J.M.M.); Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia (J.H.C.); Department of Surgery (A.W.C.) and Department of Pathology (E.W.R.), University of Washington School of Medicine, Seattle, WA; Department of Pathology and Immunology, Faculty of medicine, University of Geneva, Geneva, Switzerland (G.G.); Department of Bioengineering, University of Washington, Seattle, WA (C.M.G., M.Y.S.); Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.S.P.) Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR (N.J.R.); Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN (M.S.); Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (J.T.); Department of Medicine, Endocrine Division, Washington University, St. Louis, MO (D.A.T.); and Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado, Anshutz Medical Campus, Aurora, CO (M.C.W.-E.). Search for more papers by this author , Julie H. CampbellJulie H. Campbell From the University of Virginia, Cardiovascular Research Center, Charlottesville, VA (A.T.N., D.G.,G.K.O.); Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY (R.D.B., C.Y., J.M.M.); Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia (J.H.C.); Department of Surgery (A.W.C.) and Department of Pathology (E.W.R.), University of Washington School of Medicine, Seattle, WA; Department of Pathology and Immunology, Faculty of medicine, University of Geneva, Geneva, Switzerland (G.G.); Department of Bioengineering, University of Washington, Seattle, WA (C.M.G., M.Y.S.); Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.S.P.) Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR (N.J.R.); Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN (M.S.); Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (J.T.); Department of Medicine, Endocrine Division, Washington University, St. Louis, MO (D.A.T.); and Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado, Anshutz Medical Campus, Aurora, CO (M.C.W.-E.). Search for more papers by this author , Alexander W. ClowesAlexander W. Clowes From the University of Virginia, Cardiovascular Research Center, Charlottesville, VA (A.T.N., D.G.,G.K.O.); Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY (R.D.B., C.Y., J.M.M.); Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia (J.H.C.); Department of Surgery (A.W.C.) and Department of Pathology (E.W.R.), University of Washington School of Medicine, Seattle, WA; Department of Pathology and Immunology, Faculty of medicine, University of Geneva, Geneva, Switzerland (G.G.); Department of Bioengineering, University of Washington, Seattle, WA (C.M.G., M.Y.S.); Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.S.P.) Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR (N.J.R.); Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN (M.S.); Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (J.T.); Department of Medicine, Endocrine Division, Washington University, St. Louis, MO (D.A.T.); and Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado, Anshutz Medical Campus, Aurora, CO (M.C.W.-E.). Search for more papers by this author , Giulio GabbianiGiulio Gabbiani From the University of Virginia, Cardiovascular Research Center, Charlottesville, VA (A.T.N., D.G.,G.K.O.); Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY (R.D.B., C.Y., J.M.M.); Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia (J.H.C.); Department of Surgery (A.W.C.) and Department of Pathology (E.W.R.), University of Washington School of Medicine, Seattle, WA; Department of Pathology and Immunology, Faculty of medicine, University of Geneva, Geneva, Switzerland (G.G.); Department of Bioengineering, University of Washington, Seattle, WA (C.M.G., M.Y.S.); Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.S.P.) Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR (N.J.R.); Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN (M.S.); Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (J.T.); Department of Medicine, Endocrine Division, Washington University, St. Louis, MO (D.A.T.); and Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado, Anshutz Medical Campus, Aurora, CO (M.C.W.-E.). Search for more papers by this author , Cecilia M. GiachelliCecilia M. Giachelli From the University of Virginia, Cardiovascular Research Center, Charlottesville, VA (A.T.N., D.G.,G.K.O.); Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY (R.D.B., C.Y., J.M.M.); Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia (J.H.C.); Department of Surgery (A.W.C.) and Department of Pathology (E.W.R.), University of Washington School of Medicine, Seattle, WA; Department of Pathology and Immunology, Faculty of medicine, University of Geneva, Geneva, Switzerland (G.G.); Department of Bioengineering, University of Washington, Seattle, WA (C.M.G., M.Y.S.); Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.S.P.) Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR (N.J.R.); Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN (M.S.); Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (J.T.); Department of Medicine, Endocrine Division, Washington University, St. Louis, MO (D.A.T.); and Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado, Anshutz Medical Campus, Aurora, CO (M.C.W.-E.). Search for more papers by this author , Michael S. ParmacekMichael S. Parmacek From the University of Virginia, Cardiovascular Research Center, Charlottesville, VA (A.T.N., D.G.,G.K.O.); Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY (R.D.B., C.Y., J.M.M.); Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia (J.H.C.); Department of Surgery (A.W.C.) and Department of Pathology (E.W.R.), University of Washington School of Medicine, Seattle, WA; Department of Pathology and Immunology, Faculty of medicine, University of Geneva, Geneva, Switzerland (G.G.); Department of Bioengineering, University of Washington, Seattle, WA (C.M.G., M.Y.S.); Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.S.P.) Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR (N.J.R.); Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN (M.S.); Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (J.T.); Department of Medicine, Endocrine Division, Washington University, St. Louis, MO (D.A.T.); and Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado, Anshutz Medical Campus, Aurora, CO (M.C.W.-E.). Search for more papers by this author , Elaine W. RainesElaine W. Raines From the University of Virginia, Cardiovascular Research Center, Charlottesville, VA (A.T.N., D.G.,G.K.O.); Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY (R.D.B., C.Y., J.M.M.); Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia (J.H.C.); Department of Surgery (A.W.C.) and Department of Pathology (E.W.R.), University of Washington School of Medicine, Seattle, WA; Department of Pathology and Immunology, Faculty of medicine, University of Geneva, Geneva, Switzerland (G.G.); Department of Bioengineering, University of Washington, Seattle, WA (C.M.G., M.Y.S.); Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.S.P.) Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR (N.J.R.); Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN (M.S.); Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (J.T.); Department of Medicine, Endocrine Division, Washington University, St. Louis, MO (D.A.T.); and Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado, Anshutz Medical Campus, Aurora, CO (M.C.W.-E.). Search for more papers by this author , Nancy J. RuschNancy J. Rusch From the University of Virginia, Cardiovascular Research Center, Charlottesville, VA (A.T.N., D.G.,G.K.O.); Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY (R.D.B., C.Y., J.M.M.); Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia (J.H.C.); Department of Surgery (A.W.C.) and Department of Pathology (E.W.R.), University of Washington School of Medicine, Seattle, WA; Department of Pathology and Immunology, Faculty of medicine, University of Geneva, Geneva, Switzerland (G.G.); Department of Bioengineering, University of Washington, Seattle, WA (C.M.G., M.Y.S.); Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.S.P.) Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR (N.J.R.); Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN (M.S.); Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (J.T.); Department of Medicine, Endocrine Division, Washington University, St. Louis, MO (D.A.T.); and Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado, Anshutz Medical Campus, Aurora, CO (M.C.W.-E.). Search for more papers by this author , Mei Y. SpeerMei Y. Speer From the University of Virginia, Cardiovascular Research Center, Charlottesville, VA (A.T.N., D.G.,G.K.O.); Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY (R.D.B., C.Y., J.M.M.); Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia (J.H.C.); Department of Surgery (A.W.C.) and Department of Pathology (E.W.R.), University of Washington School of Medicine, Seattle, WA; Department of Pathology and Immunology, Faculty of medicine, University of Geneva, Geneva, Switzerland (G.G.); Department of Bioengineering, University of Washington, Seattle, WA (C.M.G., M.Y.S.); Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.S.P.) Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR (N.J.R.); Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN (M.S.); Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (J.T.); Department of Medicine, Endocrine Division, Washington University, St. Louis, MO (D.A.T.); and Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado, Anshutz Medical Campus, Aurora, CO (M.C.W.-E.). Search for more papers by this author , Michael SturekMichael Sturek From the University of Virginia, Cardiovascular Research Center, Charlottesville, VA (A.T.N., D.G.,G.K.O.); Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY (R.D.B., C.Y., J.M.M.); Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia (J.H.C.); Department of Surgery (A.W.C.) and Department of Pathology (E.W.R.), University of Washington School of Medicine, Seattle, WA; Department of Pathology and Immunology, Faculty of medicine, University of Geneva, Geneva, Switzerland (G.G.); Department of Bioengineering, University of Washington, Seattle, WA (C.M.G., M.Y.S.); Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.S.P.) Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR (N.J.R.); Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN (M.S.); Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (J.T.); Department of Medicine, Endocrine Division, Washington University, St. Louis, MO (D.A.T.); and Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado, Anshutz Medical Campus, Aurora, CO (M.C.W.-E.). Search for more papers by this author , Johan ThybergJohan Thyberg From the University of Virginia, Cardiovascular Research Center, Charlottesville, VA (A.T.N., D.G.,G.K.O.); Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY (R.D.B., C.Y., J.M.M.); Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia (J.H.C.); Department of Surgery (A.W.C.) and Department of Pathology (E.W.R.), University of Washington School of Medicine, Seattle, WA; Department of Pathology and Immunology, Faculty of medicine, University of Geneva, Geneva, Switzerland (G.G.); Department of Bioengineering, University of Washington, Seattle, WA (C.M.G., M.Y.S.); Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.S.P.) Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR (N.J.R.); Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN (M.S.); Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (J.T.); Department of Medicine, Endocrine Division, Washington University, St. Louis, MO (D.A.T.); and Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado, Anshutz Medical Campus, Aurora, CO (M.C.W.-E.). Search for more papers by this author , Dwight A. TowlerDwight A. Towler From the University of Virginia, Cardiovascular Research Center, Charlottesville, VA (A.T.N., D.G.,G.K.O.); Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY (R.D.B., C.Y., J.M.M.); Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia (J.H.C.); Department of Surgery (A.W.C.) and Department of Pathology (E.W.R.), University of Washington School of Medicine, Seattle, WA; Department of Pathology and Immunology, Faculty of medicine, University of Geneva, Geneva, Switzerland (G.G.); Department of Bioengineering, University of Washington, Seattle, WA (C.M.G., M.Y.S.); Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.S.P.) Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR (N.J.R.); Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN (M.S.); Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (J.T.); Department of Medicine, Endocrine Division, Washington University, St. Louis, MO (D.A.T.); and Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado, Anshutz Medical Campus, Aurora, CO (M.C.W.-E.). Search for more papers by this author , Mary C. Weiser-EvansMary C. Weiser-Evans From the University of Virginia, Cardiovascular Research Center, Charlottesville, VA (A.T.N., D.G.,G.K.O.); Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY (R.D.B., C.Y., J.M.M.); Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia (J.H.C.); Department of Surgery (A.W.C.) and Department of Pathology (E.W.R.), University of Washington School of Medicine, Seattle, WA; Department of Pathology and Immunology, Faculty of medicine, University of Geneva, Geneva, Switzerland (G.G.); Department of Bioengineering, University of Washington, Seattle, WA (C.M.G., M.Y.S.); Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.S.P.) Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR (N.J.R.); Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN (M.S.); Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (J.T.); Department of Medicine, Endocrine Division, Washington University, St. Louis, MO (D.A.T.); and Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado, Anshutz Medical Campus, Aurora, CO (M.C.W.-E.). Search for more papers by this author , Chen YanChen Yan From the University of Virginia, Cardiovascular Research Center, Charlottesville, VA (A.T.N., D.G.,G.K.O.); Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY (R.D.B., C.Y., J.M.M.); Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia (J.H.C.); Department of Surgery (A.W.C.) and Department of Pathology (E.W.R.), University of Washington School of Medicine, Seattle, WA; Department of Pathology and Immunology, Faculty of medicine, University of Geneva, Geneva, Switzerland (G.G.); Department of Bioengineering, University of Washington, Seattle, WA (C.M.G., M.Y.S.); Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.S.P.) Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR (N.J.R.); Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN (M.S.); Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (J.T.); Department of Medicine, Endocrine Division, Washington University, St. Louis, MO (D.A.T.); and Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado, Anshutz Medical Campus, Aurora, CO (M.C.W.-E.). Search for more papers by this author , Joseph M. MianoJoseph M. Miano From the University of Virginia, Cardiovascular Research Center, Charlottesville, VA (A.T.N., D.G.,G.K.O.); Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY (R.D.B., C.Y., J.M.M.); Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia (J.H.C.); Department of Surgery (A.W.C.) and Department of Pathology (E.W.R.), University of Washington School of Medicine, Seattle, WA; Department of Pathology and Immunology, Faculty of medicine, University of Geneva, Geneva, Switzerland (G.G.); Department of Bioengineering, University of Washington, Seattle, WA (C.M.G., M.Y.S.); Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.S.P.) Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR (N.J.R.); Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN (M.S.); Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (J.T.); Department of Medicine, Endocrine Division, Washington University, St. Louis, MO (D.A.T.); and Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado, Anshutz Medical Campus, Aurora, CO (M.C.W.-E.). Search for more papers by this author and Gary K. OwensGary K. Owens From the University of Virginia, Cardiovascular Research Center, Charlottesville, VA (A.T.N., D.G.,G.K.O.); Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY (R.D.B., C.Y., J.M.M.); Australian Institute for Bioengineering and Nanotechnology, University of Queensland, Brisbane, Australia (J.H.C.); Department of Surgery (A.W.C.) and Department of Pathology (E.W.R.), University of Washington School of Medicine, Seattle, WA; Department of Pathology and Immunology, Faculty of medicine, University of Geneva, Geneva, Switzerland (G.G.); Department of Bioengineering, University of Washington, Seattle, WA (C.M.G., M.Y.S.); Penn Cardiovascular Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (M.S.P.) Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR (N.J.R.); Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, IN (M.S.); Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden (J.T.); Department of Medicine, Endocrine Division, Washington University, St. Louis, MO (D.A.T.); and Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado, Anshutz Medical Campus, Aurora, CO (M.C.W.-E.). Search for more papers by this author Originally published23 Oct 2012https://doi.org/10.1161/CIRCRESAHA.112.281048Circulation Research. 2013;112:17–22Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2012: Previous Version 1 More than 50 years ago, smooth muscle cells (SMCs) of the carotid artery were shown to undergo dedifferentiation on ligation injury.1 Since this classical study, scores of research groups have used a variety of in vivo and in vitro model systems, as well as numerous clinical studies, to demonstrate the conversion of normally contractile vascular SMCs to a less differentiated state of proliferation, migration, and exuberant extracellular matrix secretion, a process generally referred to as phenotypic modulation or plasticity.2–6 Such changes in vascular SMC phenotype are thought to underlie many vascular occlusive diseases. However, in a recent issue of Nature Communications, Tang et al7 provide data from in vitro cell culture, flow cytometry, and lineage tracing experiments, which they believe directly challenge this long-standing and widely accepted paradigm. Specifically, these authors contend that: (1) differentiated (SM myosin heavy chain [MHC], SM MHC+) vascular SMCs are incapable of proliferation either in vivo in response to injury or in vitro in cell culture; (2) within the media of mature blood vessels there exists a small population (<10%) of undifferentiated (SM MHC−) cells that activate markers of mesenchymal stem cells, including Sox17, Sox10, and S100β, and proliferate to completely reconstitute medial cells in response to vascular injury; and (3) these so-called medial-derived multipotential vascular stem cells (MVSC) also proliferate and express several mesenchymal stem cell markers when placed in cell culture and can be induced to differentiate into neural, chondrogenic, and SMC lineages with appropriate culture methods. The authors’ bold conclusion that “MVSC activation and differentiation, instead of SMC dedifferentiation, results in the proliferative and synthetic cells in the vascular wall,” if true, would have a huge impact on our understanding of the role of SMCs in vascular injury repair and disease. Because an implicit aspect of the authors’ claims is that previous studies have been conducted on MVSCs, not SMCs, it also potentially impacts conclusions from thousands of articles using cultured SMCs as model systems. However, close examination of their results, which are in direct contradiction to a large body of published research, reveals several misinterpretations, overstatements, and technical deficiencies that seriously undermine most of their major conclusions as discussed further in this Perspective.Although extensive studies have identified mechanisms that control the process of SMC phenotypic switching in cultured cells as reviewed by Owens et al,2 there are still major ambiguities regarding the definitive identification of altered SMC phenotypes during vascular remodeling, including vascular injury–induced proliferation and atherosclerotic plaque progression, because a key feature of this process is the loss of expression of SMC-selective gene products, such as SM MHC and SM α-actin (SMαA).8 As stated by Tang et al,7 “a widely accepted explanation is that SMCs have phenotypic plasticity and that mature or contractile SMCs can dedifferentiate into proliferative and synthetic SMCs. However, this dedifferentiation process has not been directly demonstrated by tracking the fate of mature or contractile SMCs.” Indeed, we support this statement, that is, that there is a critical need for d