title: Role of human smooth muscle cell progenitors in atherosclerotic plaque development and composition.
abstract: OBJECTIVE
  We analysed the possible protective role of human endothelial (EPCs) and smooth muscle (SPCs) progenitor cells on atherosclerosis development in apoE(-/-)RAG2(-/-) mice. We determined plasma levels of SPCs in coronary patients.
  
  
  RESULTS
  ApoE(-/-)RAG2(-/-) mice received four intravenous injections of saline, 5 x 10(5) SPCs, or 5 x 10(5) EPCs every other week, one (preventive approach) or 12(curative approach) weeks after starting a high fat diet. Derived-SPC levels were quantified from blood mononuclear cells of patients with stable angina (n = 10) and acute coronary syndromes (ACS, n = 9). SPCs reduced atherosclerosis development by 42% (P < 0.001), but had no effect on lesion progression. In the SPC group, collagen and smooth muscle cell content were increased (+80%, P < 0.001, +46%, P < 0.05, respectively), and macrophage content was decreased (-41%, P < 0.05). In the curative approach, macrophage content decreased by 40.5% (P < 0.05) after SPC injection. EPC injection had no effect on atherosclerosis development or progression. Peripheral blood-derived SPC levels were reduced in patients with ACS compared with stable angina patients (P < 0.05).
  
  
  CONCLUSIONS
  We demonstrate that SPCs limit plaque development and promote changes in plaque composition towards a stable phenotype in mice. Our finding in patients suggests that reduced peripheral blood-derived SPC levels might represent a mechanism contributing to plaque destabilization.
authors.affiliation: INSERM U689, Hôpital Lariboisière, 41, Bd de la Chapelle, 75010 Paris, France.
authors.forename: Joffrey
authors.initials: J
authors.lastname: Zoll
authors.forename: Vincent
authors.initials: V
authors.lastname: Fontaine
authors.forename: Pierre
authors.initials: P
authors.lastname: Gourdy
authors.forename: Veronique
authors.initials: V
authors.lastname: Barateau
authors.forename: Jose
authors.initials: J
authors.lastname: Vilar
authors.forename: Aurelie
authors.initials: A
authors.lastname: Leroyer
authors.forename: Izolina
authors.initials: I
authors.lastname: Lopes-Kam
authors.forename: Ziad
authors.initials: Z
authors.lastname: Mallat
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Arnal
authors.forename: Patrick
authors.initials: P
authors.lastname: Henry
authors.forename: Gerard
authors.initials: G
authors.lastname: Tobelem
authors.forename: Alain
authors.initials: A
authors.lastname: Tedgui
mesh_terms: D000368:Aged; D000818:Animals; D001057:Apolipoproteins E / Q000502:physiology; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002469:Cell Separation; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology; D018450:Disease Progression; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology*
chemical_list: D001057:Apolipoproteins E; D004268:DNA-Binding Proteins; C499308:Rag2 protein, mouse