Abstract 13855: The Impact of Plasma Levels of Receptor for Advanced Glycation End-products and High Mobility Group Box 1 in Patients With Pulmonary Hypertension

Background: In pulmonary hypertension (PH), the increase of pulmonary artery pressure by vasoconstriction, remodeling of small pulmonary arteries, and chronic pulmonary thromboembolism result in right ventricular failure and ultimately death. Nuclear protein, high mobility group box 1 (HMGB1), stabilizes nucleosome, and on release into extracellular environment, HMGB1 acts as a pro-inflammatory cytokine by activating pattern recognition receptors including receptor for advanced glycation end-products (RAGE). HMGB1 is one of endogenous ligands of RAGE, and HMGB1 and RAGE are ubiquitously expressed in various organs. Several reports have recently revealed that RAGE is expressed in pulmonary artery in patients with PH, and HMGB1 contributes to migration of vascular smooth muscle cells in PH patient. The purpose of this study was to examine the clinical significance of circulating levels of HMGB1 and RAGE in patients with PH. Methods and Results: Plasma levels of HMGB1 and soluble RAGE were measured in 33 patients with PH (9 in idiopathic PH, 7 in PH related to collagen disease, 9 in chronic thromboembolic PH (CTEPH), 8 in others) and 30 normal subjects as control. Plasma levels of HMGB1 were not difference between PH patients and control subjects, however, plasma levels of soluble RAGE were significantly higher in patients with PH than in control (1464.2 vs. 831.7 pg/ml, P=0.008). Plasma soluble RAGE levels were higher in idiopathic PH (P<0.001), PH related to collagen disease (P=0.050), and CTEPH (P=0.002) than control. In addition, there was statistically significant positive correlation between pressure gradient of tricuspid valve and plasma level of soluble RAGE (R=0.403, P=0.019). Conclusions: Plasma levels of soluble RAGE, but not HMGB1, might be a novel marker which reflects the pathological conditions in patients with PH.