title: Endothelial progenitor cells in chronic obstructive pulmonary disease and emphysema.
abstract: Endothelial injury is implicated in the pathogenesis of COPD and emphysema; however the role of endothelial progenitor cells (EPCs), a marker of endothelial cell repair, and circulating endothelial cells (CECs), a marker of endothelial cell injury, in COPD and its subphenotypes is unresolved. We hypothesized that endothelial progenitor cell populations would be decreased in COPD and emphysema and that circulating endothelial cells would be increased. Associations with other subphenotypes were examined. The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50-79 years without clinical cardiovascular disease. Endothelial progenitor cell populations (CD34+KDR+ and CD34+KDR+CD133+ cells) and circulating endothelial cells (CD45dimCD31+CD146+CD133-) were measured by flow cytometry. COPD was defined by standard spirometric criteria. Emphysema was assessed qualitatively and quantitatively on CT. Full pulmonary function testing and expiratory CTs were measured in a subset. Among 257 participants, both endothelial progenitor cell populations, and particularly CD34+KDR+ endothelial progenitor cells, were reduced in COPD. The CD34+KDR+CD133+ endothelial progenitor cells were associated inversely with emphysema extent. Both endothelial progenitor cell populations were associated inversely with extent of panlobular emphysema and positively with diffusing capacity. Circulating endothelial cells were not significantly altered in COPD but were inversely associated with pulmonary microvascular blood flow on MRI. There was no consistent association of endothelial progenitor cells or circulating endothelial cells with measures of gas trapping. These data provide evidence that endothelial repair is impaired in COPD and suggest that this pathological process is specific to emphysema.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, Vermont, United States of America.
authors.forename: Margaret F
authors.identifier: http://orcid.org/0000-0001-6769-5386
authors.initials: MF
authors.lastname: Doyle
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, Vermont, United States of America.
authors.forename: Russell P
authors.initials: RP
authors.lastname: Tracy
authors.affiliation: Department of Medicine, Columbia University, New York, New York, United States of America.
authors.forename: Megha A
authors.initials: MA
authors.lastname: Parikh
authors.affiliation: Department of Radiology, University of Iowa, Iowa City, Iowa, United States of America.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Hoffman
authors.affiliation: Department of Medicine, Columbia University, New York, New York, United States of America.
authors.forename: Daichi
authors.initials: D
authors.lastname: Shimbo
authors.affiliation: Department of Radiology, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.
authors.forename: John H M
authors.initials: JH
authors.lastname: Austin
authors.affiliation: Department of Medicine, Columbia University, New York, New York, United States of America.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Smith
authors.affiliation: Department of Radiology, Hannover Medical School, Hannover, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Hueper
authors.affiliation: Department of Radiology, Hannover Medical School, Hannover, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Vogel-Claussen
authors.affiliation: Department of Cardiology, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Joao
authors.initials: J
authors.lastname: Lima
authors.affiliation: Department of Radiology, UCLA School of Medicine, Los Angeles, California, United States of America.
authors.forename: Antoinette
authors.initials: A
authors.lastname: Gomes
authors.affiliation: Division of Cardiology, UCLA School of Medicine, Los Angeles, California, United States of America.
authors.forename: Karol
authors.initials: K
authors.lastname: Watson
authors.affiliation: Penn Cardiovascular Institute Center for Clinical Epidemiology and Biostatistics Pulmonary, Allergy and Critical Care Division, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Steven
authors.initials: S
authors.lastname: Kawut
authors.affiliation: Department of Medicine, Columbia University, New York, New York, United States of America.|Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, United States of America.
authors.forename: R Graham
authors.initials: RG
authors.lastname: Barr
mesh_terms: D000368:Aged; D004646:Emphysema / Q000276:immunology / Q000473:pathology*; D066026:Endothelial Progenitor Cells / Q000276:immunology / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010991:Plethysmography; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology / Q000473:pathology*