Table 2.

Endothelial cell-derived extracellular vesicle (EC-EV) levels in lung diseases.

Disease or Condition	Model	EC-EV phenotypes	Levels	EV medium	Other major findings	Reference
PH	Patients	CD62E+ CD144+ CD31+/CD41-	↑ ↑ ↑	Plasma	• EC-MVs (CD31+/CD41- and CD144+) predict hemodynamic severity • CD45+ increased, no changes in CD41+	(Amabile et al. 2008)
	Patients	CD62E+ CD144+ CD31+/CD41-	↑ ↑	Plasma	• CD62E+ predict poor outcomes • CD45+ increased	(Amabile et al. 2009)
	Patients	CD105+	↑	Plasma	• TF+ increased • TF+ correlate with severity of PH	(Bakouboula et al. 2008)
	Patients (CTEPH)	CD105+ CD144+	↑	Plasma	CD105+ from patients stimulate increased CD105 expression in vitro, promote angiogenesis, and inhibit apoptosis in ECs	(Belik et al. 2016)
	Patients	CD62E+	↑	Plasma	• CD31/CD61+ (PMVs) and CD11b+ increased • Patients with thrombo-embolic PH had increased CD62E+ compared to non-embolic PH	(Diehl et al. 2011)
	Patients (IPAH)	CD31+/CD42b-	↑	Plasma	CD39 ectonucleotidase expression was increased on all EV populations	(Visovatti et al. 2012)
	Monocrotaline PH rat model	CD31+/CD42b-	↑	Plasma	CD31+/CD42b- increased during disease but treatment with hepatocyte growth factor reduced EVs and reversed PAH	(Chen et al. 2014)
	Hypoxic PH rat model	CD54+	─	Plasma	• CD61+ (PMVs) and erythrocyte MVs increased • No changes in CD45+ • Total EVs increased in hypoxia and total EVs impaired endothelial-dependent relaxation	(Tual-Chalot et al. 2010)
	Su5416/Hypoxia PAH rat model	Total EVs	↑	Plasma	EVs from PAH stimulate adhesion molecule expression	(Blair, Haven, and Bauer 2016)
	Monocrotaline PH murine model	Total EVs	↑	Plasma	EVs from monocrotaline-PH mice injected into healthy mice induced PH; exosomes found to be the injury-inducing population	(Aliotta et al. 2016; Aliotta et al. 2013)
ARDS	Patients	EC-EVs not assessed		Pulmonary edema fluid	Procoagulant alveolar EVs are increased in ARDS	(Bastarache et al. 2009)
	Patients	CD31+/CD41-	↑	BAL	• EC-EVs were detectable in 6/52 ARDS patients • Leukocyte EVs are increased in ARDS	(Guervilly et al. 2011)
	Patients	EC-EVs not assessed		Plasma	Phosphatidylserine+ EVs are decreased in ICU patients who develop ARDS	(Shaver et al. 2017)
	Patients & ALI murine model- LPS (IP)	CD31+/CD41-	↑	Plasma	EC pyroptosis induces MV release in a caspase-dependent manner	(Cheng et al. 2017)
	ALI murine model-LPS (IP)	CD144+ CD62E+ CD31+ CD54+	↑ ↑ ↑ ↑	Plasma	Simvastatin protects against ALI and reduces plasma EC-MV levels	(Yu et al. 2017)
	ALI rat model- LPS (IT)	CD54+	↑	Plasma	Plasma MVs from LPS-treated rats induce pulmonary inflammation	(Li et al. 2015)
	ALI murine model-LPS (IT)	EC-EVs not assessed		BAL	Alveolar macrophage and epithelial EVs are increased in ALI	(Soni et al. 2016)
	VILI murine model	CD62E+	↑	Plasma, BAL	Pathologic mechanical stretch-induced EC-MVs cause lung injury	(Letsiou et al. 2015)
	VILI murine model	CD144+ CD62E+ CD31+/CD41- CD54+	↑ ↑ ↑ ↑	Plasma	Treatment of mice with a protective agent (Tetramethylpyrazine) reduces VILI and EC-MV levels	(Pan et al. 2017)
	VILI rat model	CD31+	↑	Plasma	Lung tissue PECAM −1 (CD31) levels are reduced in VILI	(Cabrera-Benitez et al. 2015)
COPD	Patients (smokers with signs of early emphysema)	CD31+/CD42b-	↑	Plasma	76% of EC-MVs were angiotensin converting enzyme positive, indicating the pulmonary capillaries as their main source	(Gordon et al. 2011)
	Patients (stable COPD)	CD144+ CD31+/CD41- CD62E+ CD146+	↑ ↑ ↑ ─	Plasma	• CD62E+ MVs are higher in patients with frequent exacerbations	(Takahashi et al. 2012)
	Patients	CD31+/CD42- CD62E+	↑ ↑	Plasma	• CD31+/CD42- were increased in mild and severe COPD • CD62E+ were increased in severe COPD	(Thomashow et al. 2013)
	Patients	CD31+	↑	Sputum	Positive correlation of MV levels and lung damage	(Lacedonia et al. 2016)
	Patients (Smokers)	CD31+/CD42b-	↑	Plasma	EC-MV levels are not altered in COPD smokers following smoking cessation	(Strulovici-Barel et al. 2016)
	Patients (Secondhand smoke)	CD144+ CD31+/CD41- CD62E+	↑ ↑ ↑	Plasma	Secondhand smoke results in dysfunctional endothelial progenitor cell mobilization	(Heiss et al. 2008)
	Patients & cigarette smoke murine model	CD31+/CD42b-	↑	Plasma	EC-MV levels are higher in mild COPD compared to severe COPD	(Serban et al. 2016)
	Cigarette smoke (Rat model)	CD31+/CD42b-	↑	Plasma	Negative correlation between EC-MVs and dynamic compliance	(Liu et al. 2014)
OSA	Patients	CD31+/CD42b-	↑	Blood	EMVs negatively correlate with circulating EPCs	(Jelic et al. 2009)
	Patients (Minimally symptomatic OSA)	CD31+/CD41-	─	Plasma	Annexin V+, PMPs+, and CD45+ increased	(Ayers et al. 2009)
	Patients	CD31+/CD42- CD31+/Annexin V+ CD62E+	↑ ↑ ↑	Plasma	CPAP decreased CD62E+	(Yun et al. 2010)
	Patients (desaturators vs nondesaturators)	CD146+	─	Plasma	• CD66B+ and CD62L+ increased in OSA (desaturators) • OSA (desaturators)-MVs induce endothelial dysfunction	(Priou et al. 2010)
	Patients (2 week CPAP withdrawal)	CD62E+ CD31+/CD41-	↑ ─	Plasma	No changes in CD66B+, CD45+, and PMPs after a 2 week CPAP withdrawal	(Ayers et al. 2013)
	Patients	CD146+	─	Plasma	OSA-MVs carry VEGF and stimulate angiogenesis	(Tual-Chalot et al. 2014)
	Patients	EC-EVs not assessed		Plasma	CD41+ and annexin V+ increase in the evening and with severity	(Bikov et al. 2017)
	Healthy volunteers exposed to human intermittent hypoxia (IH)	Endothelial exosomes	↑	Plasma	IH-induced exosomes cause endothelial dysfunction	(Khalyfa et al. 2016)

Description of symbols: + indicates EVs positive, - indicates EVs negative, ↑ indicates increased EV levels, ─ indicates no change in EV levels.

Abbreviations: MVs; microvesicles, PMVs; platelet microvesicles, PH; Pulmonary hypertension, IPAH; Idiopathic pulmonary arterial hypertension, CTEPH; chronic thromboembolic pulmonary hypertension, ARDS; Acute respiratory distress syndrome, ALI; Acute Lung injury, VILI; ventilator-induced lung injury, BAL; Bronchoalveolar lavage, COPD; chronic obstructive pulmonary disease, OSA; obstructive sleep apnea, CPAP; continuous positive airway pressure.