{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T04:08:02Z","timestamp":1782446882850,"version":"3.54.5"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T00:00:00Z","timestamp":1670284800000},"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><jats:title>Objective<\/jats:title><jats:p>This study aims to analyze the gene expression profile of peripheral blood in different stages of myocardial infarction (MI) by transcriptome sequencing, and to study the gene expression characteristics of peripheral blood after MI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were used to identify genes and modules associated with old myocardial infarction (OMI). Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation were applied to analyze the potential functions of genes. Hub genes were identified by Random Forest Classifier. CIBERSORT was used to provide an estimate of the abundance of 22 immune cells in peripheral blood. Quantitative polymerase chain reaction (qPCR) was used to detect gene expression levels in clinical samples. The cellular components (CC) of peripheral blood were counted by an automatic hematology analyzer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Through differential gene analysis and co-expression network analysis, 11 candidate genes were obtained. A random forest classifier identified 10 hub genes. Immune cell distribution of peripheral blood was found that T cell CD4 memory resting, NK cells resting, Dendritic cells activated, Mast cells resting, Monocytes and Neutrophils were correlated with OMI. Spearman correlation analysis found that <jats:italic>PFKFB2<\/jats:italic> is related to the above immune cells. Low expression of <jats:italic>PFKFB2<\/jats:italic> in peripheral blood of OMI was detected in clinical samples, and the relationship between <jats:italic>PFKFB2<\/jats:italic> and peripheral blood immune cell counts was analyzed, which showed monocytes were associated with <jats:italic>PFKFB2<\/jats:italic> in our study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>PFKFB2<\/jats:italic> was low expressed in OMI, and related to the distribution of immune cells. <jats:italic>PFKFB2<\/jats:italic> may play a key role in reflecting the transition from AMI to OMI, and predicting the distribution of immune cells, which provided a new perspective for improving myocardial fibrosis and adverse remodeling.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2022.993579","type":"journal-article","created":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T06:45:48Z","timestamp":1670309148000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Identification of PFKFB2 as a key gene for the transition from acute to old myocardial infarction in peripheral blood"],"prefix":"10.3389","volume":"9","author":[{"given":"Xiangyu","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyao","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinzhuang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Kuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubo","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenxi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haodong","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qilin","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,12,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1093\/rheumatology\/keab269","article-title":"Epidemiology of biopsy-confirmed giant cell arteritis in Southern Sweden-an update on incidence and first prevalence estimate.","volume":"61","author":"Stamatis","year":"2021","journal-title":"Rheumatology."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1161\/circulationaha.117.033369","article-title":"Global burden of atherosclerotic cardiovascular disease in people living with HIV: systematic review and meta-analysis.","volume":"138","author":"Shah","year":"2018","journal-title":"Circulation."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1016\/j.rec.2017.11.010","article-title":"2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with St-Segment Elevation.","volume":"70","author":"Ib\u00e1nez","year":"2017","journal-title":"Rev Esp Cardiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"e002460","DOI":"10.1161\/circheartfailure.115.002460","article-title":"Mortality associated with heart failure after myocardial infarction: a contemporary community perspective.","volume":"9","author":"Gerber","year":"2016","journal-title":"Circ Heart Fail."},{"key":"B5","doi-asserted-by":"publisher","first-page":"2503","DOI":"10.1001\/jama.2010.1768","article-title":"Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population.","volume":"304","author":"de Lemos","year":"2010","journal-title":"JAMA."},{"key":"B6","doi-asserted-by":"publisher","first-page":"614","DOI":"10.1161\/circresaha.118.312706","article-title":"Established and emerging roles of biomarkers in heart failure.","volume":"123","author":"Ibrahim","year":"2018","journal-title":"Circ Res."},{"key":"B7","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.ejphar.2015.06.025","article-title":"Galectin-3 and post-myocardial infarction cardiac remodeling.","volume":"763","author":"Meijers","year":"2015","journal-title":"Eur J Pharmacol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e002656","DOI":"10.1161\/CIRCGEN.119.002656","article-title":"Peripheral blood RNA levels of and are new independent predictors of left ventricular dysfunction after acute myocardial infarction.","volume":"12","author":"Vanhaverbeke","year":"2019","journal-title":"Circ Genom Precis Med."},{"key":"B9","doi-asserted-by":"publisher","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":"B10","doi-asserted-by":"publisher","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":"B11","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1186\/1471-2105-9-559","article-title":"WGCNA: an R package for weighted correlation network analysis.","volume":"9","author":"Langfelder","year":"2008","journal-title":"BMC Bioinformatics."},{"key":"B12","doi-asserted-by":"publisher","first-page":"e618","DOI":"10.1161\/CIR.0000000000000617","article-title":"Fourth universal definition of myocardial infarction (2018).","volume":"138","author":"Thygesen","year":"2018","journal-title":"Circulation."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1923","DOI":"10.1016\/j.clinthera.2020.09.006","article-title":"The cardiac injury immune response as a target for regenerative and cellular therapies.","volume":"42","author":"Hume","year":"2020","journal-title":"Clin Therap."},{"key":"B14","doi-asserted-by":"publisher","first-page":"C7","DOI":"10.1016\/j.jacc.2005.09.068","article-title":"Pathogenesis of atherosclerosis.","volume":"47","author":"Falk","year":"2006","journal-title":"J Am Coll Cardiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1101","DOI":"10.1093\/cvr\/cvz336","article-title":"Cardiac monocytes and macrophages after myocardial infarction.","volume":"116","author":"Peet","year":"2019","journal-title":"Cardiovasc Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1093\/eurheartj\/ehx017","article-title":"Neutrophil contributions to ischaemic heart disease.","volume":"38","author":"Hoyer","year":"2017","journal-title":"Eur Heart J."},{"key":"B17","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":"B18","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.3390\/ijms22052715","article-title":"Macrophage polarization in cardiac tissue repair following myocardial infarction.","volume":"22","author":"Kim","year":"2021","journal-title":"Int J Mol Sci."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1518","DOI":"10.1016\/j.jcmg.2018.08.024","article-title":"Changes in coronary plaque composition in patients with acute myocardial infarction treated with high-intensity statin therapy (IBIS-4): a serial optical coherence tomography study.","volume":"12","author":"R\u00e4ber","year":"2019","journal-title":"JACC Cardiovasc Imaging."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1784","DOI":"10.4049\/jimmunol.1800322","article-title":"Conventional dendritic cells impair recovery after myocardial infarction.","volume":"201","author":"Lee","year":"2018","journal-title":"J Immunol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/s0014-5793","article-title":"Hypoxic regulation of the 6-Phosphofructo-2-Kinase\/Fructose-2,6-Bisphosphatase Gene Family (PFKFB-1-4) expression in Vivo.","volume":"554","author":"Minchenko","year":"2003","journal-title":"FEBS Lett."},{"key":"B22","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1536\/ihj.20-315","article-title":"HIF-1\/Akt Signaling-Activated PFKFB2 alleviates cardiac dysfunction and cardiomyocyte apoptosis in response to hypoxia.","volume":"62","author":"Gao","year":"2021","journal-title":"Int Heart J."},{"key":"B23","first-page":"97","article-title":"Some biochemical aspects of the immune macrophage.","volume":"51","author":"Hard","year":"1970","journal-title":"Br J Exp Pathol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1964","DOI":"10.4049\/jimmunol.170.4.1964","article-title":"The mitochondrial network of human neutrophils: role in chemotaxis, phagocytosis, respiratory burst activation, and commitment to apoptosis.","volume":"170","author":"Fossati","year":"2003","journal-title":"J Immunol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"581641","DOI":"10.3389\/fcell.2020.581641","article-title":"Inhibition of PFKFB3 hampers the progression of atherosclerosis and promotes plaque stability.","volume":"8","author":"Poels","year":"2020","journal-title":"Front Cell Dev Biol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"9273559","DOI":"10.1155\/2022\/9273559","article-title":"Construction of glycolytic regulator gene signature to predict the prognosis and tumor immune cell infiltration levels for prostate cancer.","volume":"2022","author":"Zhang","year":"2022","journal-title":"Comput Math Methods Med."},{"key":"B27","doi-asserted-by":"publisher","first-page":"2432","DOI":"10.1093\/eurheartj\/ehm377","article-title":"Familial aggregation of left main coronary artery disease and future risk of coronary events in asymptomatic siblings of affected patients.","volume":"28","author":"Fischer","year":"2007","journal-title":"Eur Heart J."},{"key":"B28","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1016\/s0140-6736","article-title":"Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the Interheart Study): case-control study.","volume":"364","author":"Yusuf","year":"2004","journal-title":"Lancet."}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.993579\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T06:45:54Z","timestamp":1670309154000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2022.993579\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,6]]},"references-count":28,"alternative-id":["10.3389\/fcvm.2022.993579"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2022.993579","relation":{},"ISSN":["2297-055X"],"issn-type":[{"value":"2297-055X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,6]]},"article-number":"993579"}}