Transcriptome expression profiles and regulatory networks in patients with heart failure following myocardial infarction

Abstract Background The molecular mechanisms underlying heart failure (HF) following myocardial infarction (MI) (HF-MI) remain incompletely understood, and discoveries from whole-transcriptome profiling hold significant promise for disease prevention and treatment. Methods Whole-transcriptome sequencing was performed on whole blood from post-MI patients with and without HF to analyze differentially expressed mRNAs, lncRNAs, and circRNAs, along with functional enrichment analysis. Co-expression networks linking lncRNA-mRNA and circRNA-mRNA pairs, as well as ceRNA networks involving lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA interactions, were constructed for differentially expressed (DE) RNAs. Candidate lncRNAs were validated by RT-qPCR. Transcriptional factor-lncRNA networks were constructed, and candidate relationships were verified using RIP-PCR. Results Patients with HF-MI exhibited marked elevation of NT-proBNP and significant reduction in LVEF%. Transcriptome-wide analysis revealed 228 DE-mRNAs, 700 DE-lncRNAs, and 1188 DE-circRNAs in HF-MI compared to non-heart failure patients (NHF-MI). Construction of the ceRNA network identified hsa-miR-6089 and hsa-miR-6771-5p as candidate miRNAs in the lncRNA-miRNA-mRNA network, while hsa-miR-1207-5p and hsa-miR-10392-3p were candidate miRNAs in the circRNA-miRNA-mRNA network. PVT1, SNHG5, TTN-AS1, HCP5, and OIP5-AS1 were identified as the five candidate DE-lncRNAs, with PVT1/SNHG5 showing upregulation and TTN-AS1/HCP5/OIP5-AS1 exhibiting downregulation. The transcription factor-lncRNA network primarily involves GLIS3-HCP5 and ZNF135-PVT1, with validated associative interactions. Conclusion This study systematically mapped the regulatory network of HF-MI, suggesting potential involvement of the GLIS3-HCP5 and ZNF135-PVT1 axes in HF-MI, thereby providing a basis for exploring novel therapeutic strategies.