Abstract 1180: Levels of Circulating Endothelial Microparticles Predict Hemodynamic Severity of Untreated Pulmonary Arterial Hypertension
Background: Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling and endothelial dysfunction. Microparticles (MPs) are submicron membrane fragments shed from damaged or activated cells. We hypothesized that the levels of circulating MPs will be increased in patients with PAH and will directly correlate with the severity of the disease.
Methods: Patients >18 years old with untreated pre-capillary PAH, and without other conditions associated with increased circulating MPs levels, were included in the study and underwent right heart catheterization. Circulating MPs were measured using flow cytometry in platelet-free plasma samples obtained from peripheral venous blood. Specific measurements were also obtained for endothelial MPs that were CD62e+ (E-selectin), CD144+ (VE-Cadherin), or CD31+ (PECAM) /CD41-, as well as CD41+ (Glycoprotein IIb receptor) platelet MPs, Annexin V binding apoptotic MPs, and CD45+ (LCA) leukocyte-derived MPs.
Results: Ten patients (n=4 with idiopathic PAH, n=4 with collagen vascular disease, n=1 with HIV related PAH, n=1 with chronic obstructive pulmonary disease; mean age: 51 ±5 y; 80 % female; 50% in WHO functional class III) and 15 age and gender matched healthy controls comprised the study group. Levels of endothelial CD31+ (2593±771 vs. 935±159 ev/μL, p=0.02 with Student test), CD144+ (1244±394 vs. 160±30 ev/μL, p=0.002) and CD62e+ MPs (239±67 vs. 65±12 ev/μL, p=0.004) were significantly increased in patients compared to controls, whereas no difference was observed for platelet MPs, Annexin V+ MPs, and CD45+ MPs. Both CD144+ and CD31+ endothelial MP levels correlated strongly with mean pulmonary artery pressure (respectively R=0.83, p=0.003 and R=0. 85, p=0.002) and pulmonary vascular resistance values (respectively R=0.68, p=0.03 and R=0.74, p=0.01). These relationships were not observed for other MP subgroups.
Conclusions: In subjects with PAH, levels of circulating endothelial MPs, but not other MP subpopulations, were increased compared with control subjects, and these levels correlated with hemodynamic severity of the disease. Our results identify endothelial MP levels as a potential prognostic factor and a possible novel actor in the pathophysiology of this disease.