Circulating Endothelial Microparticle Levels Predict Hemodynamic Severity of Pulmonary Hypertension

Division of Cardiology, Department of Medicine, University of California, San Francisco, 505 Parnassus Avenue, San Francisco, CA 94143-0103, USA.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 13). 06/2008; 177(11):1268-75. DOI: 10.1164/rccm.200710-1458OC
Source: PubMed


Circulating microparticles (MPs) are submicron membrane fragments shed from damaged or activated vascular cells. Endothelial MPs are a biological marker of dysfunctional endothelium. Vascular remodeling and endothelial dysfunction are involved in pulmonary hypertension (PH).
We tested the hypothesis that circulating MPs are increased in patients with PH and that identifiable subgroups of MPs predict the hemodynamic severity of this condition progression.
Patients (n = 24; age, 54 +/- 4 yr) undergoing right heart catheterization for precapillary PH without any endothelium-active vasodilator therapy participated in the study. Age- and sex-matched healthy control subjects (n = 20) were included. Endothelial (PECAM(+) [CD31(+)]/ CD41(-), VE-cadherin(+) [CD144(+)], and E-selectin(+) [CD62e(+)]), platelet (CD41(+)), leukocyte-derived (CD45(+)), and annexin V(+) MPs were measured by flow cytometry in platelet-free plasma from venous blood.
Levels of circulating endothelial PECAM(+), VE-cadherin(+), E-selectin(+), and leukocyte-derived MPs, but not platelet and annexin V(+) MPs, were increased in subjects with PH compared with control subjects (P < 0.01 each). PECAM(+) and VE-cadherin(+) MP levels significantly correlated with mean pulmonary artery pressure (r = 0.92 and r = 0.87, respectively), pulmonary vascular resistance (r = 0.78 and r = 0.73), and mean right atrial pressure (r = 0.43, and r = 0.46) and correlated inversely with cardiac index (r = -0.59 and r = -0.52). These relationships were not observed for other MP subgroups, and persisted in multivariate analysis after adjustment for confounding factors.
In subjects with precapillary PH, levels of circulating endothelial and leukocyte MPs were increased compared with control subjects. In addition, levels of PECAM(+) and VE-cadherin(+), but not E-selectin(+), endothelial MPs predicted hemodynamic severity of the disease.

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    • "In addition, there was positive correlation between pulmonary vascular resistance, right atrial pressure, cardiac index, mean PAP and CD144, CD31/CD 41 EMP. However, significant relationship was not found between EMP and WHO functional classification or six-minute walking distance (Amabile et al., 2008). In our study, CD144 or CD146 levels were statistically high in the patient group. "
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    ABSTRACT: Objective: To find out the relation between endothelial microparticles (EMPs), pulmonary arterial stiffness and thickness of pulmonary artery intima media to determine the prognosis of Eisenmenger syndrome and their correlation with echocardiographic and hemodynamic parameters. Methods: Sixteen patients with Eisenmenger syndrome and 37 control patients were included. Electron microparticles levels, angiographic and echocardiographic findings were compared. Results: Thickness of pulmonary arterial intima media and systolic and diastolic diameters of pulmonary artery were found significant in the patient group. CD144 and CD146 EMP values of patient group were statistically high. However, there was not any significant difference in pulmonary arterial strain, elasticity and stiffness. Positive significant relationship was found between pulmonary artery intima media thickness and CD144 in patient group. But there was not any significance between CD 146 and pulmonary artery intimamedia thickness. Conclusions: Invasive methods remain as the gold standard for pulmonary hypertension diagnosis, follow-up and treatment, but it is risky and can even be fatal. Our study showed that EMPs, thickness of pulmonary artery intima media and pulmonary stiffness could be novel noninvasive modalities for the follow-up pulmonary hypertensive patients.
    Biomarkers 04/2014; 19(4). DOI:10.3109/1354750X.2014.910551 · 2.26 Impact Factor
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    • "However, to our knowledge this study is the first to demonstrate that mMP themselves, can promote endothelial vesiculation. The higher numbers of eMP observed here in our in vitro model of brain inflammation was consistent with increased release of MP during inflammation observed in clinical studies [3]–[5]. Previous studies in vivo have also described worsening of pulmonary and capillary leak when treated with high numbers eMP [50]. "
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    PLoS ONE 03/2014; 9(3):e91597. DOI:10.1371/journal.pone.0091597 · 3.23 Impact Factor
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    • "Moreover, elevated levels of circulating MPs have been reported in patients (>58 years, male or female) with acute myocardial infarction and coronary artery disease [118]. Studies published by Sinning et al. [119] have shown that circulating EMPs, but not MPs of other cellular origin, are a strong predictor of cardiovascular mortality and major cardiovascular events in patients (>66 years, male or female) with coronary artery disease and pulmonary hypertension [120]. All these data may indicate that estrogen probably does not exert its protective effects on CV diseases through the EMP axis. "
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