title: Transdifferentiation of vascular smooth muscle cells to macrophage-like cells during atherogenesis.
abstract: BACKGROUND
  Atherosclerosis is a widespread and devastating disease, but the origins of cells within atherosclerotic plaques are not well defined.
  
  
  OBJECTIVE
  To investigate the specific contribution of vascular smooth muscle cells (SMCs) to atherosclerotic plaque formation by genetic inducible fate mapping in mice.
  
  
  RESULTS
  Vascular SMCs were genetically pulse-labeled using the tamoxifen-dependent Cre recombinase, CreER(T2), expressed from the endogenous SM22α locus combined with Cre-activatable reporter genes that were integrated into the ROSA26 locus. Mature SMCs in the arterial media were labeled by tamoxifen treatment of young apolipoprotein E-deficient mice before the development of atherosclerosis and then their fate was monitored in older atherosclerotic animals. We found that medial SMCs can undergo clonal expansion and convert to macrophage-like cells that have lost classic SMC marker expression and make up a major component of advanced atherosclerotic lesions.
  
  
  CONCLUSIONS
  This study provides strong in vivo evidence for smooth muscle-to-macrophage transdifferentiation and supports an important role of SMC plasticity in atherogenesis. Targeting this type of SMC phenotypic conversion might be a novel strategy for the treatment of atherosclerosis, as well as other diseases with a smooth muscle component.
authors: From the Interfakultäres Institut für Biochemie (S.F., F.E., K.S.-O., R.F.), Department of Dermatology (B.F., M.S.), and Pharmakologie, Toxikologie und Klinische Pharmazie (R.L.), University of Tübingen, Tübingen, Germany.
authors: Susanne
authors: S
authors: Feil
authors: From the Interfakultäres Institut für Biochemie (S.F., F.E., K.S.-O., R.F.), Department of Dermatology (B.F., M.S.), and Pharmakologie, Toxikologie und Klinische Pharmazie (R.L.), University of Tübingen, Tübingen, Germany.
authors: Birgit
authors: B
authors: Fehrenbacher
authors: From the Interfakultäres Institut für Biochemie (S.F., F.E., K.S.-O., R.F.), Department of Dermatology (B.F., M.S.), and Pharmakologie, Toxikologie und Klinische Pharmazie (R.L.), University of Tübingen, Tübingen, Germany.
authors: Robert
authors: R
authors: Lukowski
authors: From the Interfakultäres Institut für Biochemie (S.F., F.E., K.S.-O., R.F.), Department of Dermatology (B.F., M.S.), and Pharmakologie, Toxikologie und Klinische Pharmazie (R.L.), University of Tübingen, Tübingen, Germany.
authors: Frank
authors: F
authors: Essmann
authors: From the Interfakultäres Institut für Biochemie (S.F., F.E., K.S.-O., R.F.), Department of Dermatology (B.F., M.S.), and Pharmakologie, Toxikologie und Klinische Pharmazie (R.L.), University of Tübingen, Tübingen, Germany.
authors: Klaus
authors: K
authors: Schulze-Osthoff
authors: From the Interfakultäres Institut für Biochemie (S.F., F.E., K.S.-O., R.F.), Department of Dermatology (B.F., M.S.), and Pharmakologie, Toxikologie und Klinische Pharmazie (R.L.), University of Tübingen, Tübingen, Germany.
authors: Martin
authors: M
authors: Schaller
authors: From the Interfakultäres Institut für Biochemie (S.F., F.E., K.S.-O., R.F.), Department of Dermatology (B.F., M.S.), and Pharmakologie, Toxikologie und Klinische Pharmazie (R.L.), University of Tübingen, Tübingen, Germany. robert.feil@uni-tuebingen.de.
authors: Robert
authors: R
authors: Feil
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D054338:Cell Transdifferentiation; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology*; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology*
chemical_list: D001057:Apolipoproteins E; D008840:Microfilament Proteins; D009124:Muscle Proteins; C051615:transgelin
keywords: atherosclerosis; cell transdifferentiation; macrophages; muscle, smooth, vascular