Exploring the Potential Regulatory Mechanisms of Mitophagy in Ischemic Cardiomyopathy.

Abstract

Purpose: Ischemic cardiomyopathy (ICM) was a clinical syndrome. Long - term myocardial blood supply insufficiency, caused by coronary atherosclerotic plaque, led to myocardial nutritional disorders and atrophy. After large - scale myocardial infarction, fibrous tissue hyperplasia impaired cardiac systolic and/or diastolic functions, causing heart failure and arrhythmia. Study shows that dysregulated mitophagy can lead to cardiomyocyte death and cardiomyopathy. However, it is still uncertain how mitophagy related genes (MRGs) may affect the diagnosis of ICM.

Patients and methods: Data were obtained from public databases. Subsequently, mitochondria autophagy score-related genes (MSRGs) were obtained through Weighted Gene Co-expression Network Analysis (WGCNA). Then, an intersection was taken between MSRGs and the differentially expressed genes (DEGs) obtained from the differential expression analysis to obtain DE-MSRGs. Then, biomarkers were identified through machine learning algorithms and Receiver Operating Characteristic curve (ROC) analysis. Next, analyses of immune infiltration, molecular regulatory network, and drug prediction were carried out. Finally, Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR) was performed on the biomarkers. It provides a certain theoretical basis for the research on the mechanism of the occurrence and development of ICM.

Results: In total, 99 DE-MSRGs between ICM and control groups were gained. The four biomarkers (PPDPF, DPEP2, LTBP1, SOCS2) were acquired, and all biomarkers had good diagnostic efficacy for ICM. The content of 3 immune cells between ICM and control groups was significantly different, namely T cells, CD8+ T cells, and neutrophil, and all biomarkers were considerably positively correlated with T cells. The ceRNA network contained 4 mRNAs, 14 miRNAs, and 12 lncRNAs, and TF-mRNA network contained 32 nodes and 38 edges. Finally, 45 drugs targeting the biomarkers were predicted, such as Salmeterol, Histamine, Rotavirus vaccine, etc. Importantly, this all 4 biomarkers were higher in ICM samples in RT-qPCR analysis.

Conclusion: Our findings provided four mitophagy related biomarkers (PPDPF, DPEP2, LTBP1, and SOCS2) for diagnosis of ICM, providing a scientific reference for further studies of ICM.