Circulating progenitor cells and vascular dysfunction in chronic obstructive pulmonary disease

PLoS One. 2014 Aug 29;9(8):e106163. doi: 10.1371/journal.pone.0106163. eCollection 2014.

Abstract

Background: In chronic obstructive pulmonary disease (COPD), decreased progenitor cells and impairment of systemic vascular function have been suggested to confer higher cardiovascular risk. The origin of these changes and their relationship with alterations in the pulmonary circulation are unknown.

Objectives: To investigate whether changes in the number of circulating hematopoietic progenitor cells are associated with pulmonary hypertension or changes in endothelial function.

Methods: 62 COPD patients and 35 controls (18 non-smokers and 17 smokers) without cardiovascular risk factors other than cigarette smoking were studied. The number of circulating progenitors was measured as CD45(+)CD34(+)CD133(+) labeled cells by flow cytometry. Endothelial function was assessed by flow-mediated dilation. Markers of inflammation and angiogenesis were also measured in all subjects.

Results: Compared with controls, the number of circulating progenitor cells was reduced in COPD patients. Progenitor cells did not differ between control smokers and non-smokers. COPD patients with pulmonary hypertension showed greater number of progenitor cells than those without pulmonary hypertension. Systemic endothelial function was worse in both control smokers and COPD patients. Interleukin-6, fibrinogen, high sensitivity C-reactive protein, vascular endothelial growth factor and tumor necrosis factor were increased in COPD. In COPD patients, the number of circulating progenitor cells was inversely related to the flow-mediated dilation of systemic arteries.

Conclusions: Pulmonary and systemic vascular impairment in COPD is associated with cigarette smoking but not with the reduced number of circulating hematopoietic progenitors. The latter appears to be a consequence of the disease itself not related to smoking habit.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AC133 Antigen
  • Aged
  • Antigens, CD / metabolism
  • Antigens, CD34 / metabolism
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / physiopathology*
  • Female
  • Glycoproteins / metabolism
  • Hematopoietic Stem Cells / metabolism
  • Hematopoietic Stem Cells / pathology*
  • Humans
  • Hypertension, Pulmonary / metabolism
  • Hypertension, Pulmonary / pathology*
  • Hypertension, Pulmonary / physiopathology
  • Leukocyte Common Antigens / metabolism
  • Male
  • Middle Aged
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / pathology
  • Neovascularization, Pathologic / physiopathology
  • Peptides / metabolism
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Pulmonary Disease, Chronic Obstructive / pathology*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Smoking

Substances

  • AC133 Antigen
  • Antigens, CD
  • Antigens, CD34
  • Glycoproteins
  • PROM1 protein, human
  • Peptides
  • Leukocyte Common Antigens

Grant support

This work was supported by grants from the “Fondo de Investigación Sanitaria, Instituto de Salud Carlos III” PI05/0244 and PI10/02175; “Fundació la Marató de TV3” (04310); SEPAR 2005; and the European Union (2005-018725/Pulmotension). S. Pizarro was the recipient of a predoctoral research fellowship from Hospital Clínic. O. Tura-Ceide was the recipient of IDIBAPS-Biotrack postdoctoral fellowship and J. García-Lucio was the recipient of a predoctoral research fellowship (PFIS) from the “Instituto de Salud Carlos III.” The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.