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: 11.99). 06/2008; 177(11):1268-75. DOI: 10.1164/rccm.200710-1458OC
Source: PubMed

ABSTRACT 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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Microparticles (MPs) could be considered biomarkers of cell damage and activation as well as novel signaling structures. Since Rheumatoid Arthritis (RA) is characterized by immune and endothelial activation, the main aim of this study was to analyze MP counts in RA patients. Citrated-blood samples were obtained from 114 RA patients, 33 healthy controls (HC) and 72 individuals with marked cardiovascular (CV) risk without autoimmune manifestations (CVR). MPs were analyzed in platelet-poor plasma and different subsets were identified by their surface markers: platelet- (CD41+), endothelial- (CD146+), granulocyte- (CD66+), monocyte- (CD14+) and Tang-derived (CD3+CD31+). Disease activity (DAS28), clinical and immunological parameters as well as traditional CV risk factors (diabetes, hypertension, dyslipidemia, and obesity) were registered from clinical records and all data were integrated using Principal Component Analysis. Absolute MP number was increased in RA patients compared to HC and positively correlated with traditional CV risk factors, similar to that of CVR subjects. In addition, frequency of the different MP subsets was different in RA patients and significantly associated to disease features. Moreover, in vitro assays revealed that MPs isolated from RA patients were able to promote endothelial activation and exhibited detrimental effects on HMEC-I endothelial cell functionality. Circulating MPs from RA patients displayed quantitative and qualitative alterations that are the result of both disease-specific and traditional CV risk factors. Accordingly, this MP pool exhibited in vitro detrimental effects on endothelial cells, thus supporting their role as biomarkers of vascular damage.
    Clinical Science 11/2014; DOI:10.1042/CS20140675 · 5.63 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Flow cytometry is the most commonly used technology to measure microvesicles (MVs). Despite reported limitations of this technique, MV levels obtained using conventional flow cytometry have yielded many clinically relevant findings, such as associations with disease severity and ability to predict clinical outcomes. This study aims to determine if MV enumeration by flow cytometry correlates with a measurement of their functional capacity, as this may explain how flow cytometry generates clinically relevant results.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Circulating endothelial microparticles act as biological markers of endothelial function that reflect vascular injury. Here, we examined the hypothesis that the quantity of endothelial microparticles in the circulation is increased in patients with ischemic cerebrovascular diseases, and investigated the potential utility of various phenotypes of endothelial microparticles as specific biomarkers of endothelial cell dysfunction. We additionally focused on identifying endothelial microparticles that may be effectively utilized as biomarkers of stroke severity in acute ischemic stroke patients. In total, 129 subjects, including 68 consecutive patients with acute ischemic stroke and 61 age- and sex-matched healthy controls, were included in the study. Levels of circulating endothelial microparticles (CD144+/CD41a-, CD31+CD41a-, CD62E+, Annexin V+CD62E+) and platelet-derived microparticles (CD41a+/CD144-) in platelet-free plasma of patients and controls were measured using flow cytometry. Levels of circulating endothelial CD144+/CD41a-, CD31+CD41a-, CD62E+, and Annexin V+CD62E+microparticles, but not platelet microparticles, were significantly increased in acute ischemic stroke patients, compared with control subjects (p<0.05). Notably, levels of CD144+/CD41a- microparticles were significantly correlated with stroke severity. A mild degree of correlation was evident between Annexin V+CD62E+microparticles and stroke subtype. No association with stroke was observed for other microparticle phenotypes. Circulating endothelial microparticle amounts are increased in acute ischemic stroke patients, compared with healthy subjects. Levels of CD144+/CD41a- microparticle, but not the other phenotypes examined, may be effectively utilized as a biomarker of ischemic severity in the clinic. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Thrombosis Research 12/2014; 135(2). DOI:10.1016/j.thromres.2014.12.006 · 2.43 Impact Factor


Available from
Jun 3, 2014