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

Abstract

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 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 (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 2 CD31 1 microparticles) were quantified as activated or apoptotic. The initial cohort (n 5 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 1 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 1 / CD31 1 ratios (P , 10 24 ) and elevated CD42b 2 CD31 1 annexin V 1 EMPs (P , 10 24 ), 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.

Extracellular vesicles released in response to respiratory exposures: implications for chronic disease

“…CS exposure of mice and rats enhanced circulating endothelial-derived EV levels (Liu et al 2014;Serban et al 2016). Transient exposure of healthy humans to second-hand or mainstream CS, and chronic smoking are associated with elevated numbers of circulating endothelial-derived EV (Gordon et al 2011;Heiss et al 2008;Mobarrez et al 2014). Smoking cessation reverts the rise in endothelial-derived EV, but only in individuals in whom lung damage has not yet been established (Strulovici-Barel et al 2016).…”

“…Some investigators proposed a link between elevated circulating endothelial-derived EV and endothelial apoptosis, especially for CD62E + endothelial EV (Gordon et al 2011;Liu et al 2014;StruloviciBarel et al 2016). It was also shown that endothelial-derived EV are associated with emphysematous lung damage and diminished lung function in smokers (Gordon et al 2011;Strulovici-Barel et al 2016). …”

Mechanisms of development of multimorbidity in the elderly

“…The increase in endothelial microparticles is related to disease severity and to the degree of emphysema, and may reflect the pulmonary capillary endothelial injury as the microparticles are positive for angiotensin-converting enzyme. There is an increase in circulating endothelial microparticles is smokers who have early emphysema [102]. Endothelial microparticles are further increased during exacerbations for over 4 weeks and could contribute to the increased cardiovascular risk following these events [100].…”

Microparticles as Biomarkers of Vascular Dysfunction in Metabolic Syndrome and its Individual Components

“…For instance, other cardiovascular risks such as smoking should be considered as factors able to modify the level and the type of circulating microparticles. Whereas Grant and collaborators [74] have described reduced levels of circulating plasma-derived microvesicles (mix of microparticles and exosomes) in smokers, other workers have found an increase in endothelial-derived microparticles [75] and unchanged levels of procoagulant microparticles [76]. Moreover, in vitro exposure of macrophages to tobacco smoke can directly induce the release of a mix of microparticles and exosomes carrying gelatinolytic and collagenolytic activities, mainly through the protease MMP14.…”