Meta-analysis of differential gene expression in idiopathic pulmonary arterial hypertension

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is a subtype of pulmonary arterial hypertension and impacts both children and adults. IPAH has overall poor survival, highlighting the importance of understanding pathogenesis. We aimed to identify differentially expressed genes in the lungs of patients with IPAH to shed light on its complex genetic background.

METHODS: Search Tag Analyze Resource for NCBI's Gene Expression Omnibus (STARGEO) was utilized to identify samples. Human lung samples from patients with IPAH and healthy controls were included. Meta-analysis was conducted on genes demonstrating differential expression (p<0.05, experimental log ratio > |0.05|). Ingenuity pathway analysis (IPA) was utilized to conduct pathway analysis.

RESULTS: Top upregulated genes include HBD, HBB, ZBED1, PPFIBP1, PTPRD, and IPCEF1, which contribute to oxygen transport and utilization, cell growth, and smooth muscle migration. Top downregulated genes include BPIFB1, PROK2, NLRP12, and CAV2, which largely regulate bone morphogenic protein signaling, control cell growth and apoptosis, and regulate inflammation. Cardiac hypertrophy signaling represented the top canonical pathways associated with IPAH. Top activated upstream regulators were lipopolysaccharide and ESR1.

CONCLUSION: Changes in genes associated with cell growth, smooth muscle migration, and oxidative stress response may relate to the pathogenesis of IPAH, possibly through allowing uncontrolled cell growth and proliferation or dysregulated inflammation. Future studies should validate these findings. Identifying genes and pathways demonstrating altered expression is a preliminary step to developing targeted therapeutics.