{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T06:10:18Z","timestamp":1783923018699,"version":"3.55.0"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"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. Cardiovasc. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The early inflammatory phase (EIP, 0\u201372\u2005h) post-acute myocardial infarction (AMI) is a critical determinant of cardiac repair and clinical outcomes. However, a comprehensive understanding of the regulatory gene networks and cellular interactions that govern this decisive period remains incomplete. This study aimed to define the key transcriptional programs and immune dynamics during the EIP of AMI.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed an integrated analysis of time-series bulk RNA-sequencing (RNA-seq) datasets (GSE206281, GSE153494) from murine myocardium post-ischemia. Single-cell RNA-seq (scRNA-seq) data (GSE163129, GSE163465) from cardiac immune cells were analyzed to characterize cellular heterogeneity and intercellular communication. A multi-modal framework combining inflammatory progression scoring with weighted gene co-expression network analysis (WGCNA) was applied to identify critical modules. Hub genes were pinpointed through protein-protein interaction network analysis and intersection with inflammation-related genes (IRGs). Their association with immune infiltration was assessed, and expression was validated in an external dataset, a murine AMI model, and a human peripheral blood cohort (GSE60993).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Temporal analysis identified 160 dynamically regulated genes post-AMI, prominently enriched in myeloid leukocyte activation and extracellular matrix organization. scRNA-seq revealed a remodeled immune landscape at day 3, characterized by increased proportions of macrophages, monocytes, and neutrophils, alongside enhanced intercellular signaling via pathways such as MIF and GALECTIN. Network analysis distilled a core set of seven inflammation-associated hub genes (\n                      <jats:italic>Grn<\/jats:italic>\n                      ,\n                      <jats:italic>Igf1<\/jats:italic>\n                      ,\n                      <jats:italic>Il18<\/jats:italic>\n                      ,\n                      <jats:italic>Itgb2<\/jats:italic>\n                      ,\n                      <jats:italic>Ncf2<\/jats:italic>\n                      ,\n                      <jats:italic>Ncf4<\/jats:italic>\n                      ,\n                      <jats:italic>Spp1<\/jats:italic>\n                      ). These genes showed cell-type-specific expression patterns in myeloid subsets, correlated positively with myeloid cell infiltration in bulk tissue, and were significantly upregulated in the murine AMI model. Exploratory single-gene ROC analyses in a human peripheral blood cohort suggested preliminary differential expression trends for some hub genes (e.g., Spp1, Ncf4), but the very limited sample size precluded reliable construction of a multi-gene model and renders these findings strictly hypothesis-generating.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study delineates a high-resolution map of transcriptional and cellular dynamics during the EIP of AMI, revealing a coordinated network of inflammatory mediators linked to early myeloid cell recruitment and activation. The identified seven-candidate hub genes represents a prioritized set of candidates for future investigation into diagnostic biomarkers and therapeutic strategies targeting the early inflammatory window.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcvm.2026.1837094","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T05:33:50Z","timestamp":1783920830000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated multi-omics profiling of the early post-infarct heart reveals a hub gene network associated with myeloid-driven inflammation"],"prefix":"10.3389","volume":"13","author":[{"given":"Zeyang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiology, General Hospital of Central Theater Command of PLA","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhu","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Cardiology, General Hospital of Central Theater Command of PLA","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinchuan","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, General Hospital of Central Theater Command of PLA","place":["Wuhan, China"]},{"name":"Hubei Provincial Hospital of Traditional Chinese Medicine","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"B1","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\u20132019: update from the GBD 2019 study","volume":"76","author":"Roth","year":"2020","journal-title":"J Am Coll Cardiol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e70418","DOI":"10.1002\/mco2.70418","article-title":"Acute myocardial infarction: molecular pathogenesis, diagnosis, and clinical management","volume":"6","author":"Zhu","year":"2025","journal-title":"MedComm (2020)"},{"key":"B3","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.ijcard.2014.11.006","article-title":"The cellular immune system in the post-myocardial infarction repair process","volume":"179","author":"Latet","year":"2015","journal-title":"Int J Cardiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/nrcardio.2014.28","article-title":"The inflammatory response in myocardial injury, repair, and remodelling","volume":"11","author":"Frangogiannis","year":"2014","journal-title":"Nat Rev Cardiol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"120443","DOI":"10.1016\/j.atherosclerosis.2025.120443","article-title":"Early anti-inflammatory therapy in acute myocardial infarction: a network meta-analysis of timing-dependent effects in 23 randomized trials and 28,220 patients","volume":"408","author":"Rivero-Santana","year":"2025","journal-title":"Atherosclerosis"},{"key":"B6","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1007\/s11886-020-01358-2","article-title":"Targeting inflammation after myocardial infarction","volume":"22","author":"Mahtta","year":"2020","journal-title":"Curr Cardiol Rep"},{"key":"B7","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.pharmthera.2018.01.001","article-title":"Inflammation following acute myocardial infarction: multiple players, dynamic roles, and novel therapeutic opportunities","volume":"186","author":"Ong","year":"2018","journal-title":"Pharmacol Ther"},{"key":"B8","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1161\/CIRCRESAHA.116.303577","article-title":"The biological basis for cardiac repair after myocardial infarction: from inflammation to fibrosis","volume":"119","author":"Prabhu","year":"2016","journal-title":"Circ Res"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1718","DOI":"10.1161\/CIRCRESAHA.124.323658","article-title":"Repair of the infarcted heart: cellular effectors, molecular mechanisms and therapeutic opportunities","volume":"134","author":"Hilgendorf","year":"2024","journal-title":"Circ Res"},{"key":"B10","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1161\/CIRCRESAHA.119.315807","article-title":"Lgr4 governs a pro-inflammatory program in macrophages to antagonize post-infarction cardiac repair","volume":"127","author":"Huang","year":"2020","journal-title":"Circ Res"},{"key":"B11","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1161\/CIRCULATIONAHA.118.036044","article-title":"Dectin-1 contributes to myocardial ischemia\/reperfusion injury by regulating macrophage polarization and neutrophil infiltration","volume":"139","author":"Fan","year":"2019","journal-title":"Circulation"},{"key":"B12","doi-asserted-by":"publisher","first-page":"6672","DOI":"10.1038\/s41467-022-33631-z","article-title":"Dusp6 deficiency attenuates neutrophil-mediated cardiac damage in the acute inflammatory phase of myocardial infarction","volume":"13","author":"Zhou","year":"2022","journal-title":"Nat Commun"},{"key":"B13","doi-asserted-by":"publisher","first-page":"912454","DOI":"10.3389\/fcvm.2022.912454","article-title":"Analysis of time series gene expression and DNA methylation reveals the molecular features of myocardial infarction progression","volume":"9","author":"Han","year":"2022","journal-title":"Front Cardiovasc Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1186\/s13148-022-01267-x","article-title":"Integrative analysis of DNA methylation and gene expression reveals key molecular signatures in acute myocardial infarction","volume":"14","author":"Luo","year":"2022","journal-title":"Clin Epigenetics"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e2100752","DOI":"10.1002\/smtd.202100752","article-title":"Single-Cell RNA sequencing reveals the temporal diversity and dynamics of cardiac immunity after myocardial infarction","volume":"6","author":"Jin","year":"2022","journal-title":"Small Methods"},{"key":"B16","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1038\/s41467-020-20361-3","article-title":"Cardiomyocytes stimulate angiogenesis after ischemic injury in a ZEB2-dependent manner","volume":"12","author":"Gladka","year":"2021","journal-title":"Nat Commun"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e232","DOI":"10.1161\/CIRCRESAHA.120.317200","article-title":"Dynamics of cardiac neutrophil diversity in murine myocardial infarction","volume":"127","author":"Vafadarnejad","year":"2020","journal-title":"Circ Res"},{"key":"B18","doi-asserted-by":"publisher","first-page":"4580","DOI":"10.1038\/s41467-022-32284-2","article-title":"Spatiotemporal dynamics of macrophage heterogeneity and a potential function of Trem2(hi) macrophages in infarcted hearts","volume":"13","author":"Jung","year":"2022","journal-title":"Nat Commun"},{"key":"B19","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.omtn.2020.11.013","article-title":"Long noncoding RNA cfast regulates cardiac fibrosis","volume":"23","author":"Zhang","year":"2021","journal-title":"Mol Ther Nucleic Acids"},{"key":"B20","doi-asserted-by":"publisher","first-page":"110595","DOI":"10.1016\/j.biopha.2020.110595","article-title":"Characterisation of endogenous galectin-1 and -9 expression in monocyte and macrophage subsets under resting and inflammatory conditions","volume":"130","author":"Krautter","year":"2020","journal-title":"Biomed Pharmacother"},{"key":"B21","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1186\/s12974-018-1238-x","article-title":"Fibronectin aggregates promote features of a classically and alternatively activated phenotype in macrophages","volume":"15","author":"Sikkema","year":"2018","journal-title":"J Neuroinflammation"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e2104112","DOI":"10.1002\/smll.202104112","article-title":"Macrophage polarization modulated by NF-\u03baB in polylactide membranes-treated peritendinous adhesion","volume":"18","author":"Wang","year":"2022","journal-title":"Small"},{"key":"B23","doi-asserted-by":"publisher","first-page":"7566","DOI":"10.1111\/jcmm.14626","article-title":"FOXC1 up-regulates the expression of toll-like receptors in myocardial ischaemia","volume":"23","author":"Zhang","year":"2019","journal-title":"J Cell Mol Med"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e00211","DOI":"10.1128\/MCB.00211-17","article-title":"Reducing inflammatory cytokine production from renal collecting duct cells by inhibiting GATA2 ameliorates acute kidney injury","volume":"37","author":"Yu","year":"2017","journal-title":"Mol Cell Biol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/j.jchf.2014.10.007","article-title":"Incidence, temporal trends, and prognostic impact of heart failure complicating acute myocardial infarction. The SWEDEHEART registry (Swedish web-system for enhancement and development of evidence-based care in heart disease evaluated according to recommended therapies): a study of 199,851 patients admitted with index acute myocardial infarctions, 1996 to 2008","volume":"3","author":"Desta","year":"2015","journal-title":"JACC Heart Fail"},{"key":"B26","doi-asserted-by":"publisher","first-page":"664457","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":"B27","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1016\/j.jacc.2014.01.014","article-title":"Anti-inflammatory strategies for ventricular remodeling following ST-segment elevation acute myocardial infarction","volume":"63","author":"Seropian","year":"2014","journal-title":"J Am Coll Cardiol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"151938","DOI":"10.1016\/j.imbio.2020.151938","article-title":"\u03922 integrin gene (ITGB2) mutation spectra in Pakistani families with leukocyte adhesion deficiency type 1 (LAD1)","volume":"225","author":"Nawaz Tipu","year":"2020","journal-title":"Immunobiology"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1106120","DOI":"10.3389\/fendo.2022.1106120","article-title":"Correlation between ITGB2 expression and clinical characterization of glioma and the prognostic significance of its methylation in low-grade glioma(LGG)","volume":"13","author":"Liu","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B30","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1093\/cvr\/cvab110","article-title":"Myocardin-related transcription factor A regulates integrin beta 2 transcription to promote macrophage infiltration and cardiac hypertrophy in mice","volume":"118","author":"Liu","year":"2022","journal-title":"Cardiovasc Res"},{"key":"B31","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1186\/s11658-019-0185-6","article-title":"Expression profiles of long noncoding RNAs and messenger RNAs in the border zone of myocardial infarction in rats","volume":"24","author":"Meng","year":"2019","journal-title":"Cell Mol Biol Lett"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2097","DOI":"10.1053\/j.gastro.2018.02.016","article-title":"Clinical and genomic correlates of neutrophil reactive oxygen Species production in pediatric patients with crohn\u2019s disease","volume":"154","author":"Denson","year":"2018","journal-title":"Gastroenterology"},{"key":"B33","doi-asserted-by":"publisher","first-page":"2562","DOI":"10.3324\/haematol.2021.279889","article-title":"The NADPH oxidase NOX2 is a marker of adverse prognosis involved in chemoresistance of acute myeloid leukemias","volume":"107","author":"Paolillo","year":"2022","journal-title":"Haematologica"},{"key":"B34","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1089\/ars.2016.6675","article-title":"A reduction in intracellular reactive oxygen Species due to a mutation in NCF4 promotes autoimmune arthritis in mice","volume":"25","author":"Winter","year":"2016","journal-title":"Antioxid Redox Signal"},{"key":"B35","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1186\/s12920-021-01134-3","article-title":"Comprehensive analysis of miRNA-mRNA regulatory network and potential drugs in chronic chagasic cardiomyopathy across human and mouse","volume":"14","author":"Wu","year":"2021","journal-title":"BMC Med Genomics"},{"key":"B36","doi-asserted-by":"publisher","first-page":"206039","DOI":"10.1155\/2013\/206039","article-title":"Danger signals in the initiation of the inflammatory response after myocardial infarction","volume":"2013","author":"de Haan","year":"2013","journal-title":"Mediators Inflamm"},{"key":"B37","doi-asserted-by":"publisher","first-page":"409","DOI":"10.3390\/jcdd9120409","article-title":"Identification of hub genes in the remodeling of non-infarcted myocardium following acute myocardial infarction","volume":"9","author":"Wang","year":"2022","journal-title":"J Cardiovasc Dev Dis"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1161\/CIRCRESAHA.120.315937","article-title":"Interleukin-1 and the inflammasome as therapeutic targets in cardiovascular disease","volume":"126","author":"Abbate","year":"2020","journal-title":"Circ Res"},{"key":"B39","doi-asserted-by":"publisher","first-page":"570122","DOI":"10.3389\/fimmu.2020.570122","article-title":"Immune-Boosting, antioxidant and anti-inflammatory food supplements targeting pathogenesis of COVID-19","volume":"11","author":"Mrityunjaya","year":"2020","journal-title":"Front Immunol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1186\/s12865-020-00355-y","article-title":"Progranulin inhibits LPS-induced macrophage M1 polarization via NF-\u03baB and MAPK pathways","volume":"21","author":"Liu","year":"2020","journal-title":"BMC Immunol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"9704327","DOI":"10.1155\/2020\/9704327","article-title":"Progranulin improves acute lung injury through regulating the differentiation of regulatory T cells and interleukin-10 immunomodulation to promote macrophage polarization","volume":"2020","author":"Chen","year":"2020","journal-title":"Mediators Inflamm"},{"key":"B42","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1186\/1471-2164-10-585","article-title":"Genes and gene expression modules associated with caloric restriction and aging in the laboratory mouse","volume":"10","author":"Swindell","year":"2009","journal-title":"BMC Genomics"},{"key":"B43","doi-asserted-by":"publisher","first-page":"345","DOI":"10.20471\/acc.2016.55.03.01","article-title":"Do growth hormone and insulin-like growth factor 1 affect prognosis in patients with killip I and II class acute myocardial infarction?","volume":"55","author":"Dizdarevi\u0107-Hudi\u0107","year":"2016","journal-title":"Acta Clin Croat"},{"key":"B44","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1016\/j.atherosclerosis.2011.05.034","article-title":"Effects of insulin-like growth factor 1 in preventing acute coronary syndromes: the PRIME study","volume":"218","author":"Ruidavets","year":"2011","journal-title":"Atherosclerosis"},{"key":"B45","doi-asserted-by":"publisher","first-page":"908023","DOI":"10.3389\/fimmu.2022.908023","article-title":"G\u00f6decke A: insulin-like growth factor 1 attenuates the pro-inflammatory phenotype of neutrophils in myocardial infarction","volume":"13","author":"Nederlof","year":"2022","journal-title":"Front Immunol"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1837094\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T05:33:51Z","timestamp":1783920831000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2026.1837094\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,13]]},"references-count":45,"alternative-id":["10.3389\/fcvm.2026.1837094"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2026.1837094","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,13]]},"article-number":"1837094"}}