Inhibition of the prolyl isomerase Pin1 improves endothelial function and attenuates vascular remodelling in pulmonary hypertension by inhibiting TGF-β signalling

• DOI: 10.1007/s10456-021-09812-7
• Publication Date: 2021-08-11T09:03:07Z
• Authors: Kondababu Kurakula; Quint A. J. Hagdorn; Diederik E. van d...; Anton Vonk Noorde...; Peter ten Dijke; Rudolf A. de Boer; Harm Jan Bogaard; Marie José Goumans; Rolf M. F. Berger
• Keywords: Vascular remodelling; Inflammation; 0301 basic medicine; BMP signalling; Original Paper; Hypertension, Pulmonary; Endothelial Cells; Peptidylprolyl Isomerase; Pulmonary Artery; Vascular Remodeling; Pulmonary arterial hypertension; Rats; 3. Good health; NIMA-Interacting Peptidylprolyl Isomerase; Disease Models, Animal; 03 medical and health sciences; Endothelial cell; Transforming Growth Factor beta; Animals; Humans; TGF-beta

Abstract Pulmonary arterial hypertension (PAH) is a devastating disease, characterized by obstructive pulmonary vascular remodelling ultimately leading to right ventricular (RV) failure and death. Disturbed transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) signalling, endothelial cell dysfunction, increased proliferation of smooth muscle cells fibroblasts, inflammation contribute this abnormal remodelling. Peptidyl-prolyl isomerase Pin1 has been identified as critical driver in cells, but its role the disturbed TGF-β/BMP PAH unknown. Here, we report that expression cultured microvascular (MVECs) lung tissue patients. inhibitor, juglone significantly decreased TGF-β BMP normalized their hyper-proliferative, inflammatory phenotype. Juglone treatment reversed through reducing signalling monocrotaline + shunt-PAH rat model. Fulton index, did not affect or harm cardiac function rats with RV pressure load induced artery banding. Our study demonstrates inhibition phenotype MVECs vitro vivo, potentially modulation pathways. Selective could be novel therapeutic option for PAH.