Bioinformatics analysis combined with whole transcriptome sequencing to explore key genes and regulatory mechanisms of acute type A aortic dissection

Abstract

Traditional treatments for acute type A aortic dissection (ATAAD) are ineffective, and its mechanisms are unclear. Whole transcriptome sequencing of ATAAD and healthy control (HC) aortic tissues identified differentially expressed mRNAs (DE-mRNAs), miRNAs, long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Target genes were determined by intersecting DE-mRNAs with ATAAD-related genes. Key genes were analyzed using protein-protein interaction (PPI) analysis, machine learning, and various functional analyses including gene set enrichment analysis (GSEA), Ingenuity Pathway Analysis (IPA), and immune cell infiltration analysis. Regulatory networks and potential drugs targeting key genes were also explored. Out of 1,662 DE-mRNAs and 520 module genes, 177 target genes related to hypoxia response and energy metabolism were identified. Key genes GPD1L, PFKFB4, and PKM were found, with PKM involved in the hypoxia-inducible factor 1-alpha (HIF-1α) signaling pathway, which is crucial for ATAAD angiogenesis. Hub miRNAs hsa-miR-224-3p and hsa-miR-199b-5p, and C15orf56 were noted for their regulatory roles. Phosphoaminophosphonic Acid-Adenylate Ester could be a potential drug for targeting PFKFB4. GPD1L, PFKFB4, and PKM are key genes, with PKM significantly influencing ATAAD angiogenesis through the HIF-1α pathway.