Circulating Endothelial Microparticles as a Measure of Early Lung Destruction in Cigarette Smokers
Circulating Endothelial Microparticles as a Measure of Early Lung Destruction in Cigarette Smokers
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DOI：
10.1164/rccm.201012-2061oc
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发表时间：
2011-07-15
影响因子：
24.7
通讯作者：
Crystal, Ronald G.
中科院分区：
文献类型：
--
作者：
Gordon, Cynthia;Gudi, Kirana;Crystal, Ronald G.
原理：越来越多的证据表明肺气肿与肺毛细血管内皮细胞的原发性损失有关。血管相关疾病患者血浆内皮微粒（endothelial microparticles，EMPs）水平升高，EMPs是由活化或凋亡的内皮细胞释放的小泡。目的：评估肺功能正常但肺一氧化碳弥散量（D-LCO）降低的吸烟者血浆EMPs水平是否升高。方法：通过肺功能检查评估肺健康状况（PFT：肺功能测定、总肺容量、DLCO）和胸部X线检查;通过尿尼古丁和可替宁评估吸烟状态。EMP水平（CD 42 b（-）CD 31（+）微粒）被定量为活化或凋亡。初始队列（n = 92）包括健康非吸烟者（正常PFT）、健康吸烟者（正常PFT）和有早期肺破坏证据的吸烟者（正常肺量测定，低D-LCO）。两个前瞻性队列，然后测试：一组类似于初始队列和HIV 1（+）coherent. Measures和主要结果：健康吸烟者有轻度增加的EMP水平。值得注意的是，95%的肺功能正常、D-LCO低的吸烟者EMPs增加，CD 62（+）/CD 31（+）比值降低（P < 10（-4）），CD 42 b（-）CD 31（+）annexin V+ EMPs升高（P < 10（-4）），提示来源于内皮细胞凋亡。大多数升高的EMP是血管紧张素转换酶阳性，表明来自肺毛细血管。这两个前瞻性队列证实了最初的队列data.Conclusions：血浆EMP与凋亡的特点是吸烟者肺功能正常，但减少D-LCO升高，肺气肿的概念相一致，部分与毛细血管内皮细胞凋亡，这表明肺气肿的早期发展可能与血浆EMP水平监测。
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.