{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:38:59Z","timestamp":1785436739685,"version":"3.56.0"},"reference-count":30,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007924","name":"Bengbu Medical University","doi-asserted-by":"publisher","award":["2024byzd119"],"award-info":[{"award-number":["2024byzd119"]}],"id":[{"id":"10.13039\/501100007924","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2024byzd119"],"award-info":[{"award-number":["2024byzd119"]}],"id":[{"id":"https:\/\/ror.org\/01f8qvj05","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010814","name":"Undergraduate Innovation and Entrepreneurship Training Program","doi-asserted-by":"publisher","award":["202410367020"],"award-info":[{"award-number":["202410367020"]}],"id":[{"id":"10.13039\/501100010814","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010814","name":"Anhui Educational Committee","doi-asserted-by":"publisher","award":["2024AH051202"],"award-info":[{"award-number":["2024AH051202"]}],"id":[{"id":"10.13039\/501100010814","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010814","name":"Anhui Province Key Laboratory of Basic and Translational Research of Inflammation-Related Diseases","doi-asserted-by":"publisher","award":["YZ2024D01"],"award-info":[{"award-number":["YZ2024D01"]}],"id":[{"id":"10.13039\/501100010814","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Myocardial infarction (MI) is a leading cause of mortality worldwide. Identification of robust and translatable molecular markers remains challenging due to inter-dataset and inter-species variability. In this study, we performed a cross-species integrative analysis to identify conserved hub genes and potential therapeutic targets in MI. Analysis revealed five hub genes (IL6, SERPINE1, MMP14, PLAUR, and ENO1), which were consistently validated across human peripheral blood and multiple animal models. A multigene diagnostic model demonstrated strong predictive performance (AUC = 0.904). The model was developed to distinguish myocardial infarction (MI) samples from non-MI control samples in an independent peripheral blood dataset. Drug\u2013gene interaction analysis identified candidate therapeutic compounds. These results are computational predictions from the DGIdb database and do not represent validated therapeutic effects in myocardial infarction. These findings highlight conserved molecular mechanisms of MI and provide potential biomarkers and therapeutic targets with translational relevance.<\/jats:p>","DOI":"10.3390\/ijms27136050","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:43:14Z","timestamp":1783345394000},"page":"6050","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cross-Species Identification and Validation of Hub Genes and Potential Therapeutic Targets in Myocardial Infarction"],"prefix":"10.3390","volume":"27","author":[{"given":"Zhiyong","family":"Sheng","sequence":"first","affiliation":[{"name":"School of Life Science, Bengbu Medical University, Bengbu 233030, China"},{"name":"Anhui Province Key Laboratory of Cancer Translational Medicine, Bengbu Medical University, Bengbu 233030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Li","sequence":"additional","affiliation":[{"name":"School of Life Science, Bengbu Medical University, Bengbu 233030, China"},{"name":"Anhui Province Key Laboratory of Cancer Translational Medicine, Bengbu Medical University, Bengbu 233030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyu","family":"Bao","sequence":"additional","affiliation":[{"name":"School of Life Science, Bengbu Medical University, Bengbu 233030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medical Information and Engineering, Bengbu Medical University, Bengbu 233030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zitong","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Life Science, Bengbu Medical University, Bengbu 233030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiali","family":"Guo","sequence":"additional","affiliation":[{"name":"School of Life Science, Bengbu Medical University, Bengbu 233030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1093\/eurheartj\/ehx753","article-title":"2017 ESC Guidelines for the management of ST-segment elevation myocardial infarction","volume":"39","author":"Ibanez","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0140-6736(16)30677-8","article-title":"Acute myocardial infarction","volume":"389","author":"Reed","year":"2017","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global burden of cardiovascular diseases and risk factors, 1990\u20132019: Update from the GBD 2019 study","volume":"76","author":"Roth","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2231","DOI":"10.1016\/j.jacc.2018.08.1038","article-title":"Fourth universal definition of myocardial infarction (2018)","volume":"72","author":"Thygesen","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1002\/j.2040-4603.2015.tb00664.x","article-title":"Pathophysiology of myocardial infarction","volume":"5","author":"Frangogiannis","year":"2015","journal-title":"Compr. Physiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nrcardio.2017.161","article-title":"The NLRP3 inflammasome in acute myocardial infarction","volume":"15","author":"Toldo","year":"2018","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1016\/j.stem.2018.02.009","article-title":"Vascular tissue engineering: Progress, challenges, and clinical promise","volume":"22","author":"Song","year":"2018","journal-title":"Cell Stem Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3507","DOI":"10.1073\/pnas.1222878110","article-title":"Genomic responses in mouse models poorly mimic human inflammatory diseases","volume":"110","author":"Seok","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2946","DOI":"10.1073\/pnas.1222738110","article-title":"Conservation and divergence in the transcriptional programs of the human and mouse immune systems","volume":"110","author":"Shay","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"D607","DOI":"10.1093\/nar\/gky1131","article-title":"STRING v11: Protein\u2013protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets","volume":"47","author":"Szklarczyk","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Chin, C.-H., Chen, S.-H., Wu, H.-H., Ho, C.-W., Ko, M.-T., and Lin, C.-Y. (2014). cytoHubba: Identifying hub objects and sub-networks from complex interactome. BMC Syst. Biol., 8.","DOI":"10.1186\/1752-0509-8-S4-S11"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"D1227","DOI":"10.1093\/nar\/gkad1040","article-title":"DGIdb 5.0: Rebuilding the drug\u2013gene interaction database for precision medicine and drug discovery platforms","volume":"52","author":"Cannon","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_13","first-page":"e001636","article-title":"High levels of interleukin-6 are associated with final infarct size and adverse clinical events in patients with STEMI","volume":"8","author":"Shetelig","year":"2021","journal-title":"Open Heart"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Su, J.-H., Luo, M.-Y., Liang, N., Gong, S.-X., Chen, W., Huang, W.-Q., Tian, Y., and Wang, A.-P. (2021). Interleukin-6: A novel target for cardio-cerebrovascular diseases. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.745061"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s11883-025-01387-8","article-title":"Role of interleukin-6 in atherothrombosis and myocardial infarction","volume":"28","author":"Huse","year":"2026","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Sillen, M., and Declerck, P.J. (2020). Targeting PAI-1 in cardiovascular disease: Structural insights into PAI-1 functionality and inhibition. Front. Cardiovasc. Med., 7.","DOI":"10.3389\/fcvm.2020.622473"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/s12959-018-0166-4","article-title":"Association between plasminogen activator inhibitor-1 and cardiovascular events: A systematic review and meta-analysis","volume":"16","author":"Jung","year":"2018","journal-title":"Thromb. J."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Tanase, D.M., Valasciuc, E., Anton, I.-B., Gosav, E.M., Dima, N., Cucu, A.I., Costea, C.F., Floria, D.E., Hurjui, L.L., and Tarniceriu, C.C. (2025). Matrix metalloproteinases: Pathophysiologic implications and potential therapeutic targets in cardiovascular disease. Biomolecules, 15.","DOI":"10.3390\/biom15040598"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/nrm2821","article-title":"Regulation of cell signalling by uPAR","volume":"11","author":"Smith","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.ebiom.2019.08.045","article-title":"Cardiac troponin I autoantibody induces myocardial dysfunction by targeting ENO1","volume":"47","author":"Wu","year":"2019","journal-title":"EBioMedicine"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"579","DOI":"10.3390\/antiox14050579","article-title":"Isorhamnetin attenuates isoproterenol-induced myocardial injury by reducing ENO1 in cardiomyocytes","volume":"14","author":"Guo","year":"2025","journal-title":"Antioxidants"},{"key":"ref_22","first-page":"844","article-title":"Clinical phenotypes of heart failure with preserved ejection fraction to select preclinical animal models","volume":"7","author":"Kessler","year":"2022","journal-title":"Basic Transl. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1888","DOI":"10.1161\/CIRCRESAHA.122.320246","article-title":"Large and small animal models of heart failure with reduced ejection fraction","volume":"130","author":"Pilz","year":"2022","journal-title":"Circ. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/s41392-022-00955-7","article-title":"Inflammation and atherosclerosis: Signaling pathways and therapeutic intervention","volume":"7","author":"Kong","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_26","first-page":"170","article-title":"Mouse models of human disease: An evolutionary perspective","volume":"2016","author":"Perlman","year":"2016","journal-title":"Evol. Med. Public Health"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: An R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"D545","DOI":"10.1093\/nar\/gkaa970","article-title":"KEGG: Integrating viruses and cellular organisms","volume":"49","author":"Kanehisa","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"D1144","DOI":"10.1093\/nar\/gkaa1084","article-title":"Integration of the Drug\u2013Gene Interaction Database (DGIdb 4.0) with open crowdsource efforts","volume":"49","author":"Freshour","year":"2021","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/6050\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T14:05:57Z","timestamp":1783346757000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/13\/6050"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,6]]},"references-count":30,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27136050"],"URL":"https:\/\/doi.org\/10.3390\/ijms27136050","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,6]]}}}