Increased circulating endothelial microparticles in COPD patients: a potential biomarker for COPD exacerbation susceptibility

Abstract

RationaleThe influence of COPD exacerbation on the endothelium is not completely understood. Circulating endothelial microparticles (EMPs) are membrane vesicles in circulating blood that are shed by activated or apoptotic endothelial cells. Objective To compare EMP numbers in stable COPD patients with those during and after exacerbation. Methods We examined the EMP numbers in 80 stable COPD patients, 27 patients with exacerbated COPD, and 20 healthy non-COPD volunteers. EMPs were defined as CD144+ MPs (VE-cadherin EMPs), CD31+/CD41À MPs (PECAM EMPs), CD146 MPs (MCAM EMPs) and CD62E + EMPs (E-selectin EMPs) as analysed by FACS. Von Willebrand factor (vWF) expression was utilised to identify the origins of the EMPs. Results VE-cadherin, PECAM and E-selectin EMP numbers were significantly higher in the stable COPD patients than in the non-COPD volunteers, and they were significantly higher in the patients with exacerbated COPD than in the stable COPD patients. The majority of these increased EMPs were vWF-negative, indicating a pulmonary capillary origin. Baseline E-selectin EMP levels were significantly higher in COPD patients who experienced frequent exacerbations than in those who did not have frequent exacerbations (p<0.001). Twenty-eight days after the onset of exacerbation, E-selectin EMP levels returned to those observed in stable COPD patients, whereas PECAM EMP levels remained high. MCAM EMP numbers were not elevated in stable or exacerbated-COPD patients. Conclusions Endothelial damage, mainly in pulmonary capillaries, occurs during exacerbation and continues even after clinical symptoms disappear. Higher baseline E-selectin EMP levels may indicate COPD patients who are susceptible to exacerbation.

Endothelial Microparticles in Mild Chronic Obstructive Pulmonary Disease and Emphysema. The Multi-Ethnic Study of Atherosclerosis Chronic Obstructive Pulmonary Disease Study

“…EMPs, by contrast, directly reflect endothelial perturbation unrelated to the bone marrow. Consistent with our findings for COPD, Takahashi and coworkers (29) recently showed that CD31…”

“…Plasma EMPs are also elevated in symptomatic and asymptomatic smokers compared with nonsmokers, and among nonsmokers exposed to cigarette smoke (27,28). CD31 1 EMPs were recently associated with an isolated reduction in the diffusing capacity of carbon monoxide (DL CO ) (27) and with COPD and its exacerbations (29). The clinical relevance of the former, however, is uncertain and the power of the latter study was not adequate to examine mild COPD or emphysema.…”

“…Cell-surface or other markers that definitively label EMPs as pulmonary or systemic are, unfortunately, lacking. Recently, the absence of von Willebrand factor was proposed as a marker for alveolar capillary endothelial cells (29), as has the presence of angiotensin-converting enzyme (CD143) (27). Although we did not use these markers, three lines of reasoning suggest that the origin of the excess EMPs is pulmonary.…”

Dynamic Release and Clearance of Circulating Microparticles During Cardiac Stress

“…There was no change in CD62E+ EMPs, a marker of endothelial cell activation, 22 or CD144+ EMPs, an independent predictor of future cardiovascular events. 23 Lower concentrations of CD31+CD41− EMPs or the standard negative staining approach, 24,25 which excludes platelet-derived microparticles but may lead to inclusion of leukocyte-derived microparticles, could explain this. Alternatively, CD31+CD41− EMP release in response to stress may have distinct characteristics because different EMP subpopulations are known to be released in response to different triggers.…”

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

“…Endothelial dysfunction is one of the earliest vascular changes in atherosclerosis and proposed to actively promote atherogenesis (Gimbrone and García-Cardeña 2016). Emphysema formation in COPD patients is associated with endothelial cell stress and cell death in the pulmonary capillaries, leading to impaired vessel function (McCubbrey and Curtis 2013;Takahashi et al 2012). Endothelial damage may actively contribute to the pathogenesis of COPD (Barr 2011).…”