title: CXCL12 promotes the stabilization of atherosclerotic lesions mediated by smooth muscle progenitor cells in Apoe-deficient mice.
abstract: OBJECTIVE
  Unstable atherosclerotic lesions are prone to rupture, which leads to atherothrombosis. Chemokine (C-X-C motif) ligand 12 (CXCL12) promotes the mobilization and neointimal recruitment of smooth muscle progenitor cells (SPCs), and thereby mediates vascular repair. Moreover, treatment with SPCs stabilizes atherosclerotic lesions in mice. We investigated the role of CXCL12 in the treatment of unstable atherosclerotic lesions.
  
  
  RESULTS
  Intravenous injection of CXCL12 selectively increased the level of Sca1(+)Lin platelet derived growth factor receptor-β(+) SPCs in the circulation as determined by flow cytometry. Macrophage-rich lesions were induced by partial ligation of the carotid artery in Apoe(-/-) mice. Repeated injection of CXCL12 reduced the macrophage content, increased the number of smooth muscle cells, increased the fibrous cap thickness, and increased the collagen content in these lesions. However, CXCL12 did not alter the lesion size or the luminal diameter of the carotid artery as determined by planimetry and micro-computed tomography, respectively. Recruitment of bone marrow-derived SPCs to the lesions was increased after treatment with CXCL12 in chimeric mice that expressed SM22-LacZ in bone marrow cells as determined by quantification of the number of lesional β-galactosidase-expressing cells. CXCL12 expression was upregulated in atherosclerotic arteries after CXCL12 treatment. Silencing of arterial CXCL12 expression during atherosclerosis promoted lesion formation and reduced the lesional smooth muscle cell content in CXCL12-treated mice.
  
  
  CONCLUSIONS
  Systemic treatment with CXCL12 promotes a more stable atherosclerotic lesion phenotype and enhances the accumulation of SPCs in these lesions without promoting atherosclerosis. Thus, CXCL12-induced SPC mobilization appears a promising approach to treat unstable atherosclerosis.
authors: Experimental Vascular Medicine, Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich, Pettenkoferstr. 9, 80336 Munich, Germany.
authors: Shamima
authors: S
authors: Akhtar
authors: Felix
authors: F
authors: Gremse
authors: Fabian
authors: F
authors: Kiessling
authors: Christian
authors: C
authors: Weber
authors: Andreas
authors: A
authors: Schober
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002339:Carotid Arteries / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002340:Carotid Artery Diseases / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D054426:Chemokine CXCL2 / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D005355:Fibrosis; D005434:Flow Cytometry; D005838:Genotype; D007275:Injections, Intravenous; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D034622:RNA Interference; D013234:Stem Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D055114:X-Ray Microtomography
chemical_list: D000950:Antigens, Ly; D001057:Apolipoproteins E; D015415:Biomarkers; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D020574:Proto-Oncogene Proteins c-sis; C051615:transgelin