c-kit-immunopositive vascular progenitor cells populate human coronary in-stent restenosis but not primary atherosclerotic lesions.
Progress in the treatment of human in-stent restenosis (ISR) is hampered by an imprecise understanding of the nature of the cells that occlude vascular stents. Recent studies suggest that circulating vascular progenitor cells may mediate vascular repair and lesion formation. Moreover, functional endothelial progenitor cells appear to play a protective role in attenuating vascular lesion formation. Hence, we sought to answer two important questions: 1). Are primitive cells found in ISR lesions? 2). Is the abundance of cultured angiogenic cells (CACs) in patients with ISR different from that in patients with non-ISR lesions or normal controls? Human coronary atherectomy tissue from 13 ISR, 6 postangioplasty restenosis (RS), and 14 primary (PR) atherosclerotic lesions, as well as 15 postmortem coronary artery cross sections from young individuals without atherosclerosis, were studied. All 13 ISR and 4 of 6 RS tissue specimens contained cells that immunolabeled for the primitive cell marker c-kit and smooth muscle alpha-actin, whereas the intima and media of PR lesions and normal arteries were devoid of c-kit-immunopositive cells. The abundance of peripheral blood mononuclear cell-derived CACs was assessed in 10 patients with ISR, 6 patients with angiographically verified patent stents, and 6 individuals with no clinical evidence of coronary artery disease. CACs were less abundant in ISR patients than in non-ISR controls (13.9 +/- 3.1 vs. 22.3 +/- 6.7 cells/high-power field, P < 0.05), and both of these groups had fewer CACs than non-coronary artery disease patients (37.6 +/- 3.8, P < 0.05). These findings suggest a unique pathogenesis for ISR and RS lesions that involves c-kit-immunopositive smooth muscle cells. Moreover, the paucity of CACs in patients with ISR may contribute to the pathogenesis of ISR, perhaps because of attenuated reendothelialization.
Vascular Biology Laboratory, Division of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada K1Y4W7.
Benjamin
B
Hibbert
Yong-Xiang
YX
Chen
Edward R
ER
O'Brien
D000199:Actins / Q000378:metabolism; D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001161:Arteriosclerosis / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D002452:Cell Count; D002478:Cells, Cultured; D003327:Coronary Disease / Q000628:therapy; D023903:Coronary Restenosis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007158:Immunologic Techniques; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology*; D015607:Stents
D000199:Actins; D015415:Biomarkers; D019009:Proto-Oncogene Proteins c-kit