Abstract 12244: The Impact of Anti-angiogenic Isoform of Vascular Endothelial Growth Factor A in Patients With Pulmonary Hypertension

Abstract

Background: The primary form of pulmonary hypertension (PH) is classified as idiopathic pulmonary artery hypertension (IPAH), while the secondary disease state, including collagen disease, thromboembolism and congenital heart disease with systemic-to-pulmonary shunts. Vascular endothelial growth factor (VEGF) is a key contributor for angiogenesis and vasculogenesis, and production of VEGF is urged in PH patients due to hypoxia. Alternative splicing and proteolytic processing of VEGF-A, which is the most important member of VEGF family, produces various isoforms, including VEGF165b, which has anti-angiogenic effect. The purpose of this study was to examine the clinical significance of circulating levels of VEGF165b in patients with PH. Methods and Results: Plasma levels of VEGF165b were measured in 39 patients with PH (9 in IPAH, 7 in PH related to collagen disease, 13 in chronic thromboembolic PH (CTEPH), 10 in others including congenital heart disease) and 27 normal subjects as control. In baseline clinical characteristics, female was more frequent and body mass index was smaller in PH patients than in control. Plasma VEGF165b level in PH patients was higher than in control subjects (97.1±56.2 vs. 53.3±13.4 pg/ml, P<0.001). Especially, plasma VEGF165b level was higher in IPAH (137.1±108.1 pg/ml, P<0.001), but not in PH related to collagen disease (80.1±16.1 pg/ml), CTEPH (86.4±16.7 pg/ml), and others (88.4±9.7 pg/ml). Tricuspid regurgitation pressure gradient (TR-PG) was higher in PH patients than in control (71.9 ± 25.8 vs. 11.2 ± 11.6 mmHg, P<0.001), and TR-PG had significant positive correlation with plasma VEGF165b level (R=0.281, P=0.373). Right ventricular dimension, right ventricular fractional area change and SpO2 level were not correlated with plasma VEGF165b level. Conclusions: VAGF165b, anti-angiogenic isoform, might contribute to the pathophysiology in PH, especially in idiopathic pulmonary artery hypertension.