Circulating Endothelial Microparticles as a Measure of Early Lung Destruction in Cigarette Smokers

被引:190
作者
Gordon, Cynthia [1 ]
Gudi, Kirana [2 ]
Krause, Anja [1 ]
Sackrowitz, Rachel [2 ]
Harvey, Ben-Gary [1 ,2 ]
Strulovici-Barel, Yael [1 ]
Mezey, Jason G. [1 ,3 ]
Crystal, Ronald G. [1 ,2 ]
机构
[1] Weill Cornell Med Coll, Dept Med Genet, New York, NY 10065 USA
[2] Weill Cornell Med Coll, Dept Med, Div Pulm & Crit Care Med, New York, NY 10065 USA
[3] Cornell Univ, Dept Biol Stat & Computat Biol, Ithaca, NY USA
基金
美国国家卫生研究院;
关键词
endothelium; apoptosis; endothelium-derived factors; microcirculation; smoking; OBSTRUCTIVE PULMONARY-DISEASE; CELL-DERIVED MICROPARTICLES; ACUTE ISCHEMIC-STROKE; OBJECTIVE QUANTIFICATION; ASYMPTOMATIC SMOKERS; LEUKOCYTE ACTIVATION; COMPUTED-TOMOGRAPHY; PROGENITOR CELLS; ELEVATED LEVELS; EMPHYSEMA;
D O I
10.1164/rccm.201012-2061OC
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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 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 (D-LCO). 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 D-LCO). 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 D-LCO 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 D-LCO, 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.
引用
收藏
页码:224 / 232
页数:9
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