PMID- 35845045 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220719 IS - 2297-055X (Print) IS - 2297-055X (Electronic) IS - 2297-055X (Linking) VI - 9 DP - 2022 TI - Ferroptosis and Autophagy-Related Genes in the Pathogenesis of Ischemic Cardiomyopathy. PG - 906753 LID - 10.3389/fcvm.2022.906753 [doi] LID - 906753 AB - BACKGROUND: Obesity plays an important role in type 2 diabetes mellitus (T2DM) and myocardial infarction (MI). Ferroptosis and ferritinophagy are related to metabolic pathways, such as fatty acid metabolism and mitochondrial respiration. We aimed to investigate the ferroptosis- and autophagy-related differentially expressed genes (DEGs) that might be potential targets for MI progression. METHODS: GSE116250 was analyzed to obtain DEGs. A Venn diagram was used to obtain the overlapping ferroptosis- and autophagy-related DEGs. The enrichment pathway analysis was performed and the hub genes were obtained. Pivotal miRNAs, transcription factors, and drugs with the hub genes interactions were also predicted. The MI mice model was constructed, and qPCR analysis and single-cell sequencing were used to validate the hub genes. RESULTS: Utilizing the limma package and the Venn diagram, 26 ferroptosis-related and 29 autophagy-related DEGs were obtained. The list of ferroptosis-related DEGs was analyzed, which were involved in the cellular response to a toxic substance, cellular oxidant detoxification, and the IL-17 signaling pathway. The list of autophagy-related DEGs was involved in the regulation of autophagy, the regulation of JAK-STAT signaling pathway, and the regulation of MAPK cascade. In the protein-protein interaction network, the hub DEGs, such as IL-6, PTGS2, JUN, NQO1, NOS3, LEPR, NAMPT, CDKN2A, CDKN1A, and Snai1, were obtained. After validation using qPCR analysis in the MI mice model and single-cell sequencing, the 10 hub genes can be the potential targets for MI deterioration. CONCLUSION: The screened hub genes, IL-6, PTGS2, JUN, NQO1, NOS3, LEPR, NAMPT, CDKN2A, CDKN1A, and Snai1, may be therapeutic targets for patients with MI and may prevent adverse cardiovascular events. CI - Copyright (c) 2022 Zheng, Gao, Zhang, Cheng, Liu, Qi and Li. FAU - Zheng, Yue AU - Zheng Y AD - School of Medicine, Nankai University, Tianjin, China. AD - Department of Heart Center, The Third Central Hospital of Tianjin, Tianjin, China. AD - Nankai University Affiliated Third Center Hospital, Nankai University, Tianjin, China. AD - Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China. AD - Artificial Cell Engineering Technology Research Center, Tianjin, China. FAU - Gao, Wenqing AU - Gao W AD - School of Medicine, Nankai University, Tianjin, China. AD - Department of Heart Center, The Third Central Hospital of Tianjin, Tianjin, China. AD - Nankai University Affiliated Third Center Hospital, Nankai University, Tianjin, China. AD - Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China. AD - Artificial Cell Engineering Technology Research Center, Tianjin, China. FAU - Zhang, Qiang AU - Zhang Q AD - School of Medicine, Nankai University, Tianjin, China. AD - Department of Heart Center, The Third Central Hospital of Tianjin, Tianjin, China. AD - Nankai University Affiliated Third Center Hospital, Nankai University, Tianjin, China. AD - Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China. AD - Artificial Cell Engineering Technology Research Center, Tianjin, China. FAU - Cheng, Xian AU - Cheng X AD - School of Medicine, Nankai University, Tianjin, China. AD - Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China. AD - Artificial Cell Engineering Technology Research Center, Tianjin, China. AD - Department of Heart Center, The Third Central Clinical College of Tianjin Medical University, Tianjin, China. FAU - Liu, Yanwu AU - Liu Y AD - School of Medicine, Nankai University, Tianjin, China. AD - Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China. AD - Artificial Cell Engineering Technology Research Center, Tianjin, China. AD - Department of Heart Center, The Third Central Clinical College of Tianjin Medical University, Tianjin, China. FAU - Qi, Zhenchang AU - Qi Z AD - School of Medicine, Nankai University, Tianjin, China. AD - Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China. AD - Artificial Cell Engineering Technology Research Center, Tianjin, China. AD - Department of Heart Center, The Third Central Clinical College of Tianjin Medical University, Tianjin, China. FAU - Li, Tong AU - Li T AD - School of Medicine, Nankai University, Tianjin, China. AD - Department of Heart Center, The Third Central Hospital of Tianjin, Tianjin, China. AD - Nankai University Affiliated Third Center Hospital, Nankai University, Tianjin, China. AD - Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China. AD - Artificial Cell Engineering Technology Research Center, Tianjin, China. AD - Department of Heart Center, The Third Central Clinical College of Tianjin Medical University, Tianjin, China. LA - eng PT - Journal Article DEP - 20220630 PL - Switzerland TA - Front Cardiovasc Med JT - Frontiers in cardiovascular medicine JID - 101653388 PMC - PMC9279674 OTO - NOTNLM OT - GEO OT - IL-6 OT - autophagy OT - ferroptosis OT - myocardial infarction OT - pathway enrichment analysis OT - progression OT - single cell sequencing COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/07/19 06:00 MHDA- 2022/07/19 06:01 PMCR- 2022/01/01 CRDT- 2022/07/18 03:44 PHST- 2022/03/29 00:00 [received] PHST- 2022/05/19 00:00 [accepted] PHST- 2022/07/18 03:44 [entrez] PHST- 2022/07/19 06:00 [pubmed] PHST- 2022/07/19 06:01 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fcvm.2022.906753 [doi] PST - epublish SO - Front Cardiovasc Med. 2022 Jun 30;9:906753. doi: 10.3389/fcvm.2022.906753. eCollection 2022.