Abstract 235: Plasma Levels of Cyclophilin A Correlate with Circulating Inflammatory Cytokines in Patients with Pulmonary Hypertension
Background: Excessive proliferation and resistance to apoptosis of pulmonary artery smooth muscle cells (PASMCs) are key characteristics of pulmonary vascular remodeling in patients with pulmonary hypertension (PH). The mechanisms of pathophysiological changes in PH are not fully investigated. Cyclophilin A (CyPA) is secreted from vascular smooth muscle cells (VSMCs) in response to several stimuli, including oxidative stress, mechanical stretch and hypoxia. Extracellular CyPA and its receptor Basigin induce secretion of growth factors and inflammatory cytokines from VSMCs. Additionally, plasma CyPA levels predict poor outcome in patients with PH. In this study, we examined the correlations between plasma CyPA levels and circulating cytokines/chemokines and growth factors in PH patients.
Methods and Results: In consecutive 176 patients undergoing right heart catheterization, we examined the relationship between plasma CyPA and inflammatory cytokines/chemokines and growth factors. We used ELISA for CyPA measurement and Bio-Plex system for measurement of inflammatory cytokines/chemokines and growth factors. Plasma CyPA levels in PH patients increased according to their severity assessed by pulmonary vascular resistance (P<0.001). A positive correlation was noted between plasma CyPA levels and several inflammatory cytokines/chemokines and growth factors, including CXCL1 (P<0.001), CXCL9 (P=0.001), macrophage colony-stimulating factor (P=0.020), SDF-1α (P=0.005) and PDGF-BB (P=0.003). Interestingly, there was a significant correlation between plasma levels of CyPA and those of LDL-cholesterol (P=0.003) or HbA1c (P=0.006). In contrast, there was no correlation between CyPA and high-sensitivity CRP (P=0.172). Finally, plasma levels of CyPA and SDF-1α were significantly less in patients with statins (both P<0.01).
Conclusions: Plasma levels of CyPA are correlated with those of circulating cytokines/chemokines and growth factors, suggesting an inflammatory role of CyPA in PH patients. These data further support the crucial role of CyPA as a pathogenic molecule and a therapeutic target in PH.
Author Disclosures: T. Otsuki: None. K. Satoh: None. N. Kikuchi: None. J. Omura: None. S. Kudo: None. K. Sugimura: None. T. Aoki: None. S. Tatebe: None. H. Shimokawa: None.
- © 2015 by American Heart Association, Inc.