title: Factors associated with purity, biological function, and activation potential of endothelial colony-forming cells.
abstract: Endothelial colony-forming cells (ECFCs) are undergoing extensive investigations to tackle certain deliberating cardiovascular diseases. However, the success of this approach depends on a thorough understanding of ECFC biology. This study sought to determine the factors associated with the purity, biological function, and activation potential of ex vivo expanded ECFCs. Seventy-three patients with newly diagnosed coronary artery disease (CAD) and 24 controls were studied. ECFCs were cultured for up to 10 passages to investigate changes in and the impact of coronary risk factors on ECFC biological functions and the atherogenic potential. Passages 3-5 of ECFCs exhibited higher endothelial phenotype expression and better biological functions, in terms of nitric oxide secretion and tubular formation, but lower activation potentials compared with later passages (P <0.05). Studies on passage 3 showed that endothelial phenotype expression and biological functions were impaired, and the activation potentials of the ECFCs were significantly upregulated in subjects with coronary risk factors and especially those with CAD (P < 0.05). Furthermore, ECFCs were already activated before inflammatory stimulation in subjects with diabetes mellitus, hypertension, and CAD. Atorvastatin upregulated the endothelial nitric oxide synthase expression of ECFCs in CAD patients (P < 0.01), although not up to the baseline level of controls. In conclusion, the passage number and a variety of coronary risk factors were associated with the purity, biological function, and activation potential of ex vivo-expanded ECFCs. Functional assessments and manipulations of ECFCs have to be pursued in patients with extensive risk factors.
authors.affiliation: Heart Failure Center, Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital at Keelung, Chang Gung University College of Medicine, Taoyuan, 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: Jong-Hwei
authors.initials: JH
authors.lastname: Su Pang
authors.forename: Wen-Jin
authors.initials: WJ
authors.lastname: Cherng
authors.forename: Shing-Jong
authors.initials: SJ
authors.lastname: Lin
authors.forename: Tao-Hsin
authors.initials: TH
authors.lastname: Tung
authors.forename: Hsiu-Fu
authors.initials: HF
authors.lastname: Mei
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000378:metabolism; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010641:Phenotype; D012307:Risk Factors; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D018836:Inflammation Mediators; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III