Comprehensive network analysis to identify the molecular pathogenesis of pulmonary hypertension.

Abstract

Pulmonary hypertension (PAH) is a chronic progressive disease that may lead to right heart failure and eventually death. At present, great progress had been achieved in the treatment of pulmonary hypertension. However, pulmonary hypertension cannot be fundamentally cured, and its pathogenesis is still unclear. A multifactor-driven dysfunction module of pulmonary hypertension has been constructed in order to explore its potential pathogenesis. We performed differential expression analysis, coexpression analysis, enrichment analysis and hypergeometric test to calculate the potential regulatory effects of multiple factors on the module. Four modules and corresponding hub genes were identified. In addition, we also obtained a series of ncRNA (MALAT1 and miR-17-5p) and transcription factor (HIF1A). Network analysis revealed that MALAT1, NFKB1 and RELA targeting IL1B of module 4 and IL6 of module 1 to participate in the occurrence and development of pulmonary hypertension through Toll-like receptor signaling pathway. It is necessary to identify disease-related disorders by integrating multiple regulatory factors. The regulatory network may play an important role in PAH. The results not only provided new methods and ideas for follow-up research, but also helps researchers to have a deeper understanding of potential pathogenesis for PAH.