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59 Endothelial colony forming cells (ECFC) are senescent and dysfunctional in COPD due to reduced sirtuin-1 levels
  1. K Paschalaki1,
  2. R D Starke2,
  3. N Mercado1,
  4. D O Haskard2,
  5. P J Barnes1,
  6. A M Randi2
  1. 1Airway Disease Department, NHLI, Imperial College, London, UK
  2. 2Cardiovascular Sciences, NHLI, Imperial College, London, UK

Abstract

Introduction Cardiovascular disease (CVD) is a major cause of death in chronic obstructive pulmonary disease (COPD). Numerous studies describe clinical evidence of endothelial dysfunction in COPD but the molecular pathways which link COPD and CVD remain unclear. Endothelial colony forming cells (ECFC) could serve as a research tool to investigate endothelial defects in COPD patients.

Aim and Objectives To examine whether ECFC from COPD patients exhibit dysfunctional characteristics, illustrating the underlying molecular process of endothelial dysfunction in COPD.

Methods ECFC were isolated from peripheral blood samples received from 16 healthy non-smoking volunteers (age±SEM, 57±2.7 yr), 10 healthy smokers (57±2.6 yr) and 16 COPD patients (67±1.6 yr). The mononuclear fraction was placed in culture in the presence of endothelial growth factors. ECFC appeared between day 7 and 24, as characteristic cobblestone monolayers. The cells were grown to confluence in T-25 or T-75 flasks and used at passages 4 to 6 for all experiments. Endothelial senescence was measured by senescence-associated β-galactosidase (SA-β-Gal) activity and sirtuin (SIRT) 1 protein levels by Western blotting.

Results ECFC from healthy smokers and COPD patients displayed significantly increased senescence and reduced SIRT1 protein levels compared to healthy non-smoking subjects. SIRT1 protein levels negatively correlated with endothelial senescence.

Conclusions The results from our study demonstrate that ECFC from smokers and COPD patients display epigenetic molecular dysfunctions linked to increased senescence. These defects may contribute to endothelial dysfunction and cardiovascular events.

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