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

Am J Respir Crit Care Med. 2011 Jul 15;184(2):224-32. doi: 10.1164/rccm.201012-2061OC. Epub 2011 Mar 11.


Rationale: There is increasing evidence that emphysema is 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 vascular-related 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 (Dl(co)).

Methods: Lung health was assessed by pulmonary function tests (PFTs: spirometry, total lung capacity, Dl(co)) 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 Dl(co)). 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 Dl(co) 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 Dl(co), 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Apoptosis / drug effects
  • Biomarkers / blood
  • Cell-Derived Microparticles / drug effects*
  • Cohort Studies
  • Endothelial Cells / drug effects
  • Endothelium, Vascular / drug effects*
  • Female
  • Forced Expiratory Volume
  • Humans
  • Lung Injury / blood*
  • Lung Injury / chemically induced
  • Lung Injury / diagnostic imaging
  • Male
  • Middle Aged
  • Prospective Studies
  • Radiography
  • Respiratory Function Tests / methods
  • Smoking / adverse effects*
  • Smoking / blood*
  • Spirometry


  • Biomarkers