Endostatin and Vascular Endothelial Growth Factor-A₁₆₅b May Contribute to Classification of Pulmonary Hypertension

Pulmonary hypertension (PH) is characterized by dysregulation of small pulmonary arteries. In addition to endostatin (ES), placenta growth factor (PlGF), vascular endothelial growth factor-A (VEGF-A), and the anti-angiogenesis isoform of VEGF-A (VEGF-A₁₆₅b) are associated with PH. However, the usefulness of these biomarkers in PH in unknown. We investigated whether these 4 biomarkers are related to PH classification. Between July 2015 and August 2017, 33 control patients and 107 PH patients were enrolled in the study. Among the PH patients, 48 had pulmonary arterial hypertension (PAH), 5 had left heart disease-associated PH (LHD-PH), 4 had lung disease-associated PH (LD-PH), and 50 had chronic thromboembolic PH (CTEPH). Among the PAH patients, 16 had idiopathic PAH (IPAH) and 17 had connective tissue disease-associated PAH (CTD-PAH). PlGF, total VEGF-A, and VEGF-A₁₆₅b levels were measured in the control and PH groups. ES was only measured in the PH group. VEGF-A₁₆₅b levels were significantly higher in the LD-PH group than in the PAH, LHD-PH, and CTEPH groups (all P<0.001). PlGF levels were significantly higher in the CTD-PAH group than in the IPAH and control groups. ES levels were significantly correlated with the 6-min walk distance (P<0.001), B-type natriuretic peptide (P<0.001), and pulmonary vascular resistance (P=0.008). ES could detect CTD-PAH in PAH and may be an indicator of PH severity. VEGF-A₁₆₅b was useful in detecting LD-PH.