title: Differentiation profile of peripheral blood-derived vascular progenitor cell predicts intimal hyperplasia after coronary stenting.
abstract: In-stent restenosis is largely due to intimal hyperplasia (IH). The number of vascular progenitor cells (VPCs) mobilized at the acute phase after stenting is associated with IH. This study sought to determine whether the differentiation profile of VPC predicts the development of IH. Peripheral blood was collected in 58 patients after bare-metal stenting to culture VPCs. Intravascular ultrasound was performed to estimate the area of IH 6 months after stenting. VPC differentiation was determined using flow cytometry. VE-cadherin (VE-Cad) and α-smooth muscle actin (α-SMA) were used to identify endothelial and smooth muscle cell lineages, respectively. After culturing, VPCs differentiated into four different phenotypes (α-SMA(-)VE-Cad(+), α-SMA(+)VE-cad(high), α-SMA(+)VE-cad(low), and α-SMA(+)VE-Cad(-)). IH was correlated with gender (P = 0.04), smoking status (P = 0.04), reference diameter (P = 0.03), minimal lumen diameter (P = 0.03), stent area (P < 0.0001), and parameters in the VPC differentiation profile (P < 0.05). Multivariate analysis controlling for stent area, smoking status, and gender revealed that IH was positively and independently associated with the number of differentiated α-SMA(+)VE-Cad (low/-) VPCs (P < 0.0001), and the ratio of α-SMA(+)VE-Cad (low/-) VPCs to α-SMA(-)VE-Cad(+) VPCs (P = 0.001). These parameters in the VPC differentiation profile independently predicted the IH and provided additive information to traditional risk factors. In conclusion, the profile of VPC differentiation predicts the severity of post-stent IH and may be a potential tool in the future for clinicians to identify patients at risk of post-stent restenosis.
authors.affiliation: Heart Failure Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, 222 Mai Chin Road, Keelung, Taiwan. bearty@adm.cgmh.org.tw
authors.forename: Chao-Hung
authors.initials: CH
authors.lastname: Wang
authors.forename: I-Chang
authors.initials: IC
authors.lastname: Hsieh
authors.forename: Wen-Jin
authors.initials: WJ
authors.lastname: Cherng
authors.forename: Chun-Chi
authors.initials: CC
authors.lastname: Chen
authors.forename: Tao-Hsin
authors.initials: TH
authors.lastname: Tung
authors.forename: Ju-Fang
authors.initials: JF
authors.lastname: Lee
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Lin
authors.forename: Po-Nan
authors.initials: PN
authors.lastname: Wang
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects* / Q000295:instrumentation*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D023903:Coronary Restenosis / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000473:pathology*; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D006965:Hyperplasia; D016014:Linear Models; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D015999:Multivariate Analysis; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D010641:Phenotype; D018570:Risk Assessment; D012307:Risk Factors; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D015607:Stents; D013624:Taiwan; D013997:Time Factors; D016896:Treatment Outcome; D017539:Tunica Intima / Q000000981:diagnostic imaging / Q000473:pathology*; D018084:Ultrasonography, Interventional; D057772:Vascular System Injuries / Q000473:pathology
chemical_list: D015415:Biomarkers