Analysis of the prognostic value of mitochondria-related genes in patients with acute myocardial infarction.

ABSTRACT

BACKGROUND: Acute myocardial infarction (AMI) is a leading cause of death worldwide. Mitochondrial dysfunction is a key determinant of cell death post-AMI. Preventing mitochondrial dysfunction is thus a key therapeutic strategy. This study aimed to explore key genes and target compounds related to mitochondrial dysfunction in AMI patients and their association with major adverse cardiovascular events (MACE). METHODS: Differentially expressed genes in AMI were identified from the Gene Expression Omnibus (GEO) datasets (GSE166780 and GSE24519), and mitochondria-related genes were obtained from MitoCarta3.0 database. By intersection of the two gene groups, mitochondria-related genes in AMI were identified. Next, the identified genes related to mitochondria were subject to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses. Protein-protein interaction (PPI) network was constructed, and key genes were screened. Then, targeted drug screening and molecular docking were performed. Blood samples from AMI patients and healthy volunteers were analyzed for the key genes expressions using quantitative real time polymerase chain reaction (qRT-PCR). Later, receiver operating characteristic (ROC) curves assessed the diagnostic value of key genes, and univariate and multivariate COX analyses identified risk factors and protective factors for MACE in AMI patients. RESULTS: After screening and identification, 138 mitochondria-related genes were identified, mainly enriched in the processes and pathways of cellular respiration, redox, mitochondrial metabolism, apoptosis, amino acid and fatty acid metabolism. According to the PPI network, 5 key mitochondria-related genes in AMI were obtained translational activator of cytochrome c oxidase I (TACO1), cytochrome c oxidase subunit Va (COX5A), PTEN-induced putative kinase 1 (PINK1), SURF1, and NDUFA11. Molecular docking showed that Cholic Acid, N-Formylmethionine interacted with COX5A, nicotinamide adenine dinucleotide + hydrogen (NADH) and NDUFA11. Subsequent basic experiments revealed that COX5A and NDUFA11 expressions were significantly lower in the blood of patients with AMI than those in the corresponding healthy volunteers; also, AMI patients with MACE had lower COX5A and NDUFA11 expressions in the blood than those without MACE (P < 0.01). ROC analysis also showed high diagnostic value for COX5A and NDUFA11 [area under the curve (AUC) > 0.85]. In terms of COX results, COX5A, NDUFA11 and left ventricular ejection fraction (LVEF) were protective factors for MACE in AMI, while C-reactive protein (CRP) was a risk factor. CONCLUSION: COX5A and NDUFA11, key mitochondria-related genes in AMI, may be used as biomarkers to diagnose AMI and predict MACE.