{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:25:16Z","timestamp":1787502316637,"version":"build-2736575974"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T00:00:00Z","timestamp":1783555200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Myocardial infarction (MI) remains a leading cause of cardiovascular mortality worldwide, underscoring the need for improved diagnostic and therapeutic strategies. Despite recent in clinical management, delayed diagnosis and complications such as adverse myocardial remodeling continue to compromise long-term outcomes. Identifying specific biomarkers and actionable therapeutic targets is therefore crucial for precision medicine in MI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We integrated MI-related datasets from the Gene Expression Omnibus (GEO) database and performed differential expression analysis alongside weighted gene co-expression network analysis (WGCNA) to identify key differentially expressed genes (DEGs). Machine learning algorithms were applied to screen diagnostic hub genes and evaluate their diagnostic performance. Two-sample Mendelian randomization (MR) analysis, primarily utilizing the random-effects inverse-variance weighting assessed causal relationships between candidate genes and MI risk. Immune profiling was conducted via immune cell infiltration deconvolution and scRNA-seq analysis. Finally, wet-lab validation was performed using quantitative real-time PCR (RT-qPCR), Western blot, and immunohistochemistry in an\n                      <jats:italic>in vivo<\/jats:italic>\n                      animal model.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Our analysis initially identified 15 key diagnostic genes. Through two-sample MR analysis, MYO6 exhibited a significant causal relationship with a reduced risk of MI. Immune infiltration analysis revealed significant enrichment of pro-inflammatory cells (neutrophils and monocytes) and a concomitant depletion of protective immune cells (resting natural killer cells and activated CD4 memory T cells) in MI patients. MYO6 expression correlated positively with protective immune cells and negatively with pro-inflammatory cells. Furthermore, scRNA-seq analysis showed that MYO6 was predominantly enriched in T cells and natural killer cells, potentially regulating their subset differentiation, inhibiting excessive intercellular communication, and promoting collagen-mediated tissue repair, thereby alleviating MI injury and enhancing plaque stability.\n                      <jats:italic>In vivo<\/jats:italic>\n                      experiments validated the successful establishment of the MI model, revealing that MYO6 was significantly downregulated at both the mRNA and protein levels in infarcted myocardium.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Through multidimensional analysis of clinical transcriptomic data and experimental validation in animal models, we have identified MYO6 as a potential novel diagnostic biomarker for MI, while highlighting the role of immune homeostasis in disease progression and MYO6 regulation. These findings provide crucial insights for the molecular diagnosis and targeted therapy of MI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1797028","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:19:20Z","timestamp":1783570760000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Uncovering the pivotal role of MYO6 in myocardial infarction: a multimodally validated diagnostic biomarker and immunotherapeutic target"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiawei","family":"Wang","sequence":"first","affiliation":[{"name":"School of Pharmacy, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiguo","family":"Lei","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daiqian","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifeng","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Qu","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Zou","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jjcc.2022.07.003","article-title":"Treatment strategies of acute myocardial infarction: updates on revascularization, pharmacological therapy, and beyond","volume":"81","author":"Saito","year":"2022","journal-title":"J Cardiol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2982","DOI":"10.1016\/j.jacc.2020.11.010","article-title":"Global burden of cardiovascular diseases and risk factors, 1990-2019: update from the GBD 2019 study","volume":"76","author":"Roth","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.123.029971","article-title":"Acute myocardial infarction: etiologies and mimickers in young patients","volume":"12","author":"Krittanawong","year":"2023","journal-title":"J Am Heart Assoc"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.123.067097","article-title":"Advanced cardiac patches for the treatment of myocardial infarction","volume":"149","author":"Liu","year":"2024","journal-title":"Circulation"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1172\/jci159498","article-title":"Mitochondrial dysfunction in macrophages promotes inflammation and suppresses repair after myocardial infarction","volume":"133","author":"Cai","year":"2023","journal-title":"J Clin Invest"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.664457","article-title":"Cells of the immune system in cardiac remodeling: main players in resolution of inflammation and repair after myocardial infarction","volume":"12","author":"Kologrivova","year":"2021","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1097295","article-title":"Immune cells drive new immunomodulatory therapies for myocardial infarction: from basic to clinical translation","volume":"14","author":"Nian","year":"2023","journal-title":"Front Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00230.2022","article-title":"Macrophages in myocardial infarction","volume":"323","author":"Kubota","year":"2022","journal-title":"Am J Physiol Cell Physiol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvz336","article-title":"Cardiac monocytes and macrophages after myocardial infarction","volume":"116","author":"Peet","year":"2020","journal-title":"Cardiovasc Res"},{"key":"B10","doi-asserted-by":"publisher","first-page":"6480","DOI":"10.1038\/s41467-024-50806-y","article-title":"Tregs delivered post-myocardial infarction adopt an injury-specific phenotype promoting cardiac repair via macrophages in mice","volume":"15","author":"Alshoubaki","year":"2024","journal-title":"Nat Commun"},{"key":"B11","doi-asserted-by":"publisher","first-page":"101398","DOI":"10.1016\/j.cpcardiol.2022.101398","article-title":"Novel therapeutic strategies to reduce reperfusion injury after acute myocardial infarction","volume":"47","author":"Sch\u00e4fer","year":"2022","journal-title":"Curr Probl Cardiol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"7301","DOI":"10.3390\/ijms21197301","article-title":"Preconditioned and genetically modified stem cells for myocardial infarction treatment","volume":"21","author":"Raziyeva","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.2147\/vhrm.s9108","article-title":"Coronary computed tomographic angiography (CCTA) in community hospitals: \"current and emerging role","volume":"6","author":"Sharma","year":"2010","journal-title":"Vasc Healt Risk Manage"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.2147\/vhrm.s327661","article-title":"The main causes and mechanisms of increase in cardiac troponin concentrations other than acute myocardial infarction (part 1): physical exertion, inflammatory heart disease, pulmonary embolism, renal failure, sepsis","volume":"17","author":"Chauin","year":"2021","journal-title":"Vasc Healt Risk Manage"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-024-01883-0","article-title":"High-dimensional single-cell analysis of human natural killer cell heterogeneity","volume":"25","author":"Rebuffet","year":"2024","journal-title":"Nat Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3343\/alm.2020.40.1.7","article-title":"Performance of copeptin for early diagnosis of acute myocardial infarction in an emergency department setting","volume":"40","author":"Jeong","year":"2020","journal-title":"Ann Lab Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.14740\/cr1652","article-title":"FASLG as a key member of necroptosis participats in acute myocardial infarction by regulating immune infiltration","volume":"15","author":"Jia","year":"2024","journal-title":"Cardiol Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.5579","article-title":"KLRF1, a novel marker of CD56bright NK cells, predicts improved survival for patients with locally advanced bladder cancer","volume":"12","author":"Mukherjee","year":"2022","journal-title":"Cancer Med"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.13025","article-title":"Amelioration of inflammatory myopathies by glucagon-like peptide-1 receptor agonist via suppressing muscle fibre necroptosis","volume":"13","author":"Kamiya","year":"2022","journal-title":"J Cachexia Sarcopenia Muscle"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2025-011636","article-title":"Single-cell RNA sequencing of baseline PBMCs predicts ICI efficacy and irAE severity in patients with NSCLC","volume":"13","author":"Kim","year":"2025","journal-title":"J Immunother Cancer"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20190546","article-title":"IL2RB maintains immune harmony","volume":"216","author":"Campbell","year":"2019","journal-title":"J Exp Med"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.936707","article-title":"Identification of immune hub genes participating in the pathogenesis and progression of Vogt-Koyanagi-Harada disease","volume":"13","author":"Wang","year":"2022","journal-title":"Front Immunol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.ra119.011400","article-title":"PYHIN1 regulates pro-inflammatory cytokine induction rather than innate immune DNA sensing in airway epithelial cells","volume":"295","author":"Massa","year":"2020","journal-title":"J Biol Chem"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2114134119","article-title":"PDGF-D-PDGFR\u03b2 signaling enhances IL-15-mediated human natural killer cell survival","volume":"119","author":"Ma","year":"2022","journal-title":"Proc Natl Acad Sci USA"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12294","article-title":"MicroRNA-125b modulates inflammatory chemokine CCL4 expression in immune cells and its reduction causes CCL4 increase with age","volume":"14","author":"Cheng","year":"2015","journal-title":"Aging Cell"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1097\/cm9.0000000000002808","article-title":"Effects of COL1A1 and SYTL2 on inflammatory cell infiltration and poor extracellular matrix remodeling of the vascular wall in thoracic aortic aneurysm","volume":"137","author":"Xie","year":"2023","journal-title":"Chin Med J"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.91396","article-title":"Carbonic anhydrase 3 is required for cardiac repair post myocardial infarction via Smad7-Smad2\/3 signaling pathway","volume":"20","author":"Su","year":"2024","journal-title":"Int J Biol Sci"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.101526","article-title":"Structure and function of the ecto-nucleotide pyrophosphatase\/phosphodiesterase (ENPP) family: tidying up diversity","volume":"298","author":"Borza","year":"2021","journal-title":"J Biol Chem"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1567466","article-title":"Machine learning combined multi-omics analysis to explore key oxidative stress features in systemic lupus erythematosus","volume":"16","author":"Zhou","year":"2025","journal-title":"Front Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.13486","article-title":"The MYO6 interactome: selective motor-cargo complexes for diverse cellular processes","volume":"593","author":"de Jonge","year":"2019","journal-title":"FEBS Lett"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2025.1599746","article-title":"Herb pair of Astragali Radix-Descurainiae Semen attenuate heart failure through the myosin VI-Tom1 complex mediated autophagy","volume":"12","author":"Wang","year":"2025","journal-title":"Front Cardiovasc Med"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.05.048","article-title":"MYO6 regulates spatial organization of signaling endosomes driving AKT activation and actin dynamics","volume":"19","author":"Masters","year":"2017","journal-title":"Cell Rep"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s11897-015-0255-7","article-title":"Cellular immunity and cardiac remodeling after myocardial infarction: role of neutrophils, monocytes, and macrophages","volume":"12","author":"Shinagawa","year":"2015","journal-title":"Curr Heart Fail Rep"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1797028\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:19:21Z","timestamp":1783570761000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1797028\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,9]]},"references-count":33,"alternative-id":["10.3389\/fimmu.2026.1797028"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1797028","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,9]]},"article-number":"1797028"}}