Table 2 Summary of studies on the mechanism of endothelial extracellular vesicles in COPD
From: Extracellular vesicles and chronic obstructive pulmonary disease (COPD): a systematic review
Mechanism—endothelial cells | ||||
|---|---|---|---|---|
Author, year [Ref.] | Title | Aim | Type | Conclusion |
Takahashi et al., 2013 [17] | Differences in the released endothelial microparticle subtypes between pulmonary microvascular endothelial cells and aortic endothelial cells in vitro | Evaluate the effects of common stimuli involved in COPD on endothelial microparticles (EMPs) released. Investigate whether increased circulating EMP subtypes reflect the degree and site of endothelial injury in COPD patients | In vitro | H2O2 and cigarette smoke extract (CSE) induced apoptosis, resulting in the release of PECAM EMPs from pulmonary ECs and MCAM EMPs from both pulmonary and aortic EC types. TNF-a stimulation resulted in EC activation, resulting in the upregulation of E-selectin, a mechanism that occurs during COPD exacerbation. Thus, EMP subtypes reflect differences among stimuli and site of injury in COPD mechanism |
Strulovici-Barel et al., 2016 [18] | Persistence of circulating endothelial microparticles in COPD despite smoking cessation | Investigate whether elevated levels of circulating apoptotic EMPs persists in COPD smokers following smoking cessation, reflecting continuous lung endothelial injury that persists even after the stress of smoking is removed | Ex vivo Human | Total pulmonary capillary EMP levels were highest in healthy smokers, followed by COPD smokers, when compared to non-smokers, with 48% of healthy smokers and 45% of COPD smokers showing increased levels of apoptotic EMPs. This suggests active pulmonary capillary apoptosis ongoing in both healthy and COPD smokers that persisted even after they stopped smoking following their baseline assessment |
Thomashow et al., 2013 [19] | Endothelial microparticles in mild chronic obstructive pulmonary disease and emphysema | Examine the relationships of circulating levels of EMPs with COPD | Ex vivo Human | CD31+ EMPs were elevated in COPD and were positively related to percent emphysema. Additionally, CD62E+ EMPs were elevated in severe COPD and with hyperinflation. These cellular markers may implicate endothelial apoptosis in the pathogenesis of COPD and emphysema |
Garcia-Lucio et al., 2018 [20] | Imbalance between endothelial damage and repair capacity in chronic obstructive pulmonary disease | Investigate whether COPD patients have an imbalance between EMPs to PCs (progenitor cells) compared to non-smokers and current smokers. Evaluate the effect of cigarette smoke on these circulating markers | Ex vivo Human | COPD patients presented a significantly disturbed ratio of elevated circulating apoptotic EMP levels with reduced bone marrow-derived PC numbers, reflecting an imbalance between endothelial damage and reduced repair capacity |
Barak et al., 2017 [21] | Disturbed blood flow worsens endothelial dysfunction in moderate-severe chronic obstructive pulmonary disease | To test whether oscillatory shear stress further exacerbates endothelial dysfunction in patients with moderate-severe COPD and to observe any potential link between chronic hypoxemia and EMPs in COPD | In vivo/ex vivo Human | In moderate-severe COPD patients, acutely disturbed blood flow further deteriorates endothelial dysfunction that is compounded with increases in circulating MPs indicative of endothelial apoptosis (CD31+/CD41b−), and is of greater consequence given the already impaired vasculature of this population |
Liu et al., 2014 [22] | Circulating endothelial microparticles involved in lung function decline in a rat exposed in cigarette smoke maybe from apoptotic pulmonary capillary endothelial cells | Investigate if the number of EMPs is elevated in rats exposed in cigarette smoke, and whether the elevated EMPs are derived from pulmonary capillaries | In vivo Mice | Exposure of rats to CS resulted in high levels of circulating CD42b/CD31+ EMPs (cEMPs), which increased with an increase in time of exposure. High levels of CD42b/CD31+ cEMPs reflected the decline of small airway function indirectly in early COPD and would be useful for evaluating the degree of COPD progression |
Nieri et al., 2021 [23] | Circulating extracellular vesicles are associated with disease severity and interleukin-6 levels in COPD: a Pilot study | Analyse endothelial-(E) and monocyte-derived (M) EV levels in COPD patients grouped according to the 2011 GOLD classification and analyse the relationship between EV and plasmatic markers of inflammation | Ex vivo Human | Circulating endothelial- and monocyte-derived extracellular vesicles increase along with COPD severity. The relationship among EEV and IL-6 suggests a biological link between inflammation and endothelial activation/damage |
Lascano et al., 2021 [24] | Association of systemic endothelial-derived and platelet-derived microparticles with clinical outcomes in chronic obstructive pulmonary disease | Analyse whether eMPs and pMPs are associated with COPD status and/or severity | Ex vivo Human | Most MPs measured do not correlate significantly with COPD status, COPD severity, or exacerbations in our cohort. The apoptotic eMP 62E+/eMP 31+  ratio may be a useful marker of early endothelium apoptosis and early recognition of the disease process. Platelet activation assessed by pMP 41+31+ increases with disease severity and may be an important feature for stage 4 COPD patients |