title: Human endothelial progenitor cells isolated from COPD patients are dysfunctional.
abstract: Cardiovascular disease is the leading cause of morbidity and mortality in patients with moderate-to-severe chronic obstructive pulmonary disease (COPD). More than 44% of these patients present with generalized atherosclerosis at autopsy. It is accepted that endothelial progenitor cells (EPCs) participate in the repair of dysfunctional endothelium and thus protects against atherosclerosis. However, whether COPD affects the repairing capacity of EPCs is unknown. Therefore, the objective of this study was to determine whether and how EPCs are involved in the vascular repair process in patients with COPD. In our study, EPCs from 25 COPD and 16 control patients were isolated by Ficoll density-gradient centrifugation and identified using fluorescence activated cell sorting. Transwell Migratory Assay was performed to determine the number of EPC colony-forming units and the adherent capacity late-EPCs to human umbilical vein endothelial cells. Following arterial damage in NOD/SCID mice, the number of EPCs incorporated at the injured vascular site was determined using a fluorescence microscope. We found that the number of EPC clusters and cell migration, as well as the expression of CXCR4, was significantly decreased in patients with COPD. Additionally, the number of late-EPCs adherent to HUVEC tubules was significantly reduced, and fewer VEGFR2(+)-staining cells were incorporated into the injured site in COPD patients. Our study demonstrates that EPC capacity of repair was affected in COPD patients, which may contribute to altered vascular endothelium in this patient population.
authors.affiliation: Respiratory Department, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan Road, Guangzhou 51008, Guangdong Province, People's Republic of China. liuxiaoran3192@163.com
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Liu
authors.forename: Canmao
authors.initials: C
authors.lastname: Xie
mesh_terms: D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D002448:Cell Adhesion; D049109:Cell Proliferation; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D002499:Centrifugation, Density Gradient; D002633:Chemotaxis; D002681:China; D003114:Colony-Forming Units Assay; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology* / Q000637:transplantation; D005263:Femoral Artery / Q000293:injuries / Q000473:pathology; D005434:Flow Cytometry; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism / Q000473:pathology*; D019718:Receptors, CXCR4 / Q000378:metabolism; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D057772:Vascular System Injuries / Q000473:pathology / Q000601:surgery
chemical_list: C527276:CXCR4 protein, human; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019718:Receptors, CXCR4; D040301:Vascular Endothelial Growth Factor Receptor-2