Integrated Transcriptomic and Metabolomic Analysis of Rat PASMCs Reveals the Underlying Mechanism for Pulmonary Arterial Hypertension

BACKGROUND: Pulmonary arterial hypertension (PAH) is a kind of pulmonary vascular lesion characterized by vasoconstriction and reshaping of small pulmonary arteries, ultimately resulting in increased pulmonary artery pressure and pulmonary vascular resistance, and eventually leading to right ventricular failure and death. This study was aimed to construct a platelet-derived growth factor BB (PDGF-BB)-induced rat pulmonary artery smooth muscle cells (PASMCs) model and conduct a combined transcriptomic and metabolomic analysis to identify proliferation-related targets, thereby enhancing the understanding of the pathogenesis underlying PAH. METHODS: Rat PASMCs were isolated and cultured in the presence or absence of PDGF-BB for 24 hours. Cells were collected for transcriptomics and metabolomics investigations. RESULTS: A total of 1,288 differentially expressed genes (DEGs; 572 upregulated and 716 downregulated) were identified in PDGF-BB-treated rat PASMCs compared with control cells. Subsequently, Gene ontology (GO) enrichment analysis revealed that 791 enriched GO terms were significantly enriched in PDGF-BB treated cells. Similarly, 294 differential metabolic pathways were enriched in PDGF-BB-treated cells according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Set Enrichment Analysis was performed on the DEGs. It turned out that 7,219 gene sets were more enriched in PDGF-BB treated cells. In addition, a total of 28 secondary differential metabolites were identified in PDGF-BB-treated rat PASMCs compared with control cells (P-value < 0.05 and VIP > 1). CONCLUSIONS: We speculate that Mylk, Pla2g4a, Gucy1b1, Adcy8, Adcy4, Gucy1a2, Col3a1, and Plcb4 are potential targets for the treatment of PAH.