Research Paper|Volume 13, Issue 10|pp 14234—14257

Integrated bioinformatic analysis reveals the underlying molecular mechanism of and potential drugs for pulmonary arterial hypertension

Haoru Dong², Xiuchun Li¹, Mengsi Cai¹, Chi Zhang², Weiqi Mao², Ying Wang², Qian Xu², Mayun Chen¹, Liangxing Wang¹, Xiaoying Huang¹

¹Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou 325000, Zhejiang, P.R. China
²The First Clinical Medical College, Wenzhou Medical University, Wenzhou 325000, Zhejiang, P.R. China

* Equal contribution

Received: November 18, 2020Accepted: March 4, 2021Published: May 18, 2021

https://doi.org/10.18632/aging.203040

Copyright: © 2021 Dong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Pulmonary arterial hypertension (PAH) is a devastating cardiovascular disease without a clear mechanism or drugs for treatment. Therefore, it is crucial to reveal the underlying molecular mechanism and identify potential drugs for PAH. In this study, we first integrated three human lung tissue datasets (GSE113439, GSE53408, GSE117261) from GEO. A total of 151 differentially expressed genes (DEGs) were screened, followed by KEGG and GO enrichment analyses and PPI network construction. Five hub genes (CSF3R, NT5E, ANGPT2, FGF7, and CXCL9) were identified by Cytoscape (Cytohubba). GSEA and GSVA were performed for each hub gene to uncover the potential mechanism. Moreover, to repurpose known and therapeutic drugs, the CMap database was retrieved, and nine candidate compounds (lypressin, ruxolitinib, triclabendazole, L-BSO, tiaprofenic acid, AT-9283, QL-X-138, huperzine-a, and L-741742) with a high level of confidence were obtained. Then ruxolitinib was selected to perform molecular docking simulations with ANGPT2, FGF7, NT5E, CSF3R, JAK1, JAK2, JAK3, TYK2. A certain concentration of ruxolitinib could inhibit the proliferation and migration of rat pulmonary artery smooth muscle cells (rPASMCs) in vitro. Together, these analyses principally identified CSF3R, NT5E, ANGPT2, FGF7 and CXCL9 as candidate biomarkers of PAH, and ruxolitinib might exert promising therapeutic action for PAH.