Circulating endothelial microparticles as a measure of early lung destruction in cigarette smokers

Cynthia Gordon, Kirana Gudi, Anja Krause, Rachel Sackrowitz, Ben Gary Harvey, Yael Strulovici-Barel, Jason G. Mezey, Ronald Crystal

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125 Citations (Scopus)

Abstract

Rationale: There is increasing evidence thatemphysemais associated with primary loss of pulmonary capillary endothelium. Plasma levels of endothelial microparticles (EMPs), small vesicles released from activated or apoptotic endothelial cells, are elevated in vascularrelated disorders. Objectives: To evaluate whether plasma EMP levels are elevated in smokers with early lung destruction as assessed by normal spirometry but reduced diffusing capacity of the lung for carbon monoxide (DLCO). Methods: Lung health was assessed by pulmonary function tests (PFTs: spirometry, total lung capacity, DLCO) and chest X-ray; smoking status was assessed by urine nicotine and cotinine. EMP levels (CD42b-CD31+ microparticles) were quantified as activated or apoptotic. The initial cohort (n = 92) included healthy nonsmokers (normal PFTs), healthy smokers (normal PFTs), and smokers with early evidence of lung destruction (normal spirometry, low DLCO). Two prospective cohorts were then tested: a group similar to the initial cohort and an HIV1+ cohort. Measurements and Main Results: Healthy smokers had mildly increased levels of EMPs. Strikingly, 95% of smokers with normal spirometry, low DLCO had increased EMPs, with reduced CD62+/CD31+ ratios (P < 10-4) and elevated CD42b-CD31+ annexin V+ EMPs (P <10-4), suggesting derivation from endothelial apoptosis. Most elevated EMPs were angiotensin-converting enzyme positive, suggesting derivation from pulmonary capillaries. Both prospective cohorts confirmed the initial cohort data. Conclusions: Plasma EMPs with apoptotic characteristics are elevated in smokers with normal spirometry but reduced DLCO, consistent with the concept that emphysema is associated, in part, with capillary endothelium apoptosis, suggesting that the early development of emphysema might be monitored with plasma EMP levels.

Original languageEnglish
Pages (from-to)224-232
Number of pages9
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume184
Issue number2
DOIs
Publication statusPublished - 15 Jul 2011
Externally publishedYes

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Keywords

  • Apoptosis
  • Endothelium
  • Endothelium-derived factors
  • Microcirculation
  • Smoking

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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