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Identification of Novel Therapeutic Targets for Pulmonary Arterial Hypertension.

Research paper by Kimio K Satoh, Nobuhiro N Kikuchi, Taijyu T Satoh, Ryo R Kurosawa, Shinichiro S Sunamura, Mohammad Abdul Hai MAH Siddique, Junichi J Omura, Nobuhiro N Yaoita, Hiroaki H Shimokawa

Indexed on: 20 Dec '18Published on: 20 Dec '18Published in: International journal of molecular sciences



Abstract

Pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) are fatal diseases; however, their pathogenesis still remains to be elucidated. We have recently screened novel pathogenic molecules and have performed drug discovery targeting those molecules. Pulmonary artery smooth muscle cells (PASMCs) in patients with PAH (PAH-PASMCs) have high proliferative properties like cancer cells, which leads to thickening and narrowing of distal pulmonary arteries. Thus, we conducted a comprehensive analysis of PAH-PASMCs and lung tissues to search for novel pathogenic proteins. We validated the pathogenic role of the selected proteins by using tissue-specific knockout mice. To confirm its clinical significance, we used patient-derived blood samples to evaluate the potential as a biomarker for diagnosis and prognosis. Finally, we conducted a high throughput screening and found inhibitors for the pathogenic proteins.