Development of Early Diagnosis and Therapeutic Agent for CTEPH Focused on a Novel Pathogenic Protein TAFI

Abstract

Plasma levels of TAFI (also known as carboxypeptidase B2, coded by CPB2) were significantly elevated in CTEPH patients. Additionally, we found that the minor allele CPB2 is present in those patients. TAFI-overexpressing mice exhibited increased right ventricular systolic pressure, RV hypertrophy, and pulmonary artery thrombus formation compared with controls. Three-dimensional computed tomography showed that TAFI-overexpressing mice had multiple pulmonary artery obstructions, which were similar to those of CTEPH patients. Finally, we performed in silico screening and found several activated TAFI inhibitors and fibrates, with which we found significant amelioration of hypoxia-induced pulmonary hypertension and improved prognosis in TAFI-overexpressing mice.