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.
|Number of pages||9|
|Journal||American Journal of Respiratory and Critical Care Medicine|
|Publication status||Published - 15 Jul 2011|
- Endothelium-derived factors
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
- Critical Care and Intensive Care Medicine