{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:36:16Z","timestamp":1760402176862,"version":"build-2065373602"},"reference-count":69,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T00:00:00Z","timestamp":1642032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004955","name":"Austrian Research Promotion Agency","doi-asserted-by":"publisher","award":["852748","862068","888225"],"award-info":[{"award-number":["852748","862068","888225"]}],"id":[{"id":"10.13039\/501100004955","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Vienna Business Agency","award":["2343727"],"award-info":[{"award-number":["2343727"]}]},{"name":"Aposcience AG","award":["HJA"],"award-info":[{"award-number":["HJA"]}]},{"name":"Christian Doppler Laboratory for Diagnosis and Regeneration of Cardiac and Thoracic Diseases","award":["HJA"],"award-info":[{"award-number":["HJA"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Acute myocardial infarction (AMI) is a result of cardiac non-perfusion and leads to cardiomyocyte necrosis, inflammation, and compromised cardiac performance. Here, we showed that the secretome of \u03b3-irradiated peripheral blood mononuclear cells (PBMCsec) improved heart function in a porcine AMI model and displayed beneficial long- and short-term effects. As an AMI is known to strongly affect gene regulation of the ischemia non-affected heart muscle and distal organs, we employed a transcriptomics approach to further study the immediate molecular events orchestrated using the PBMCsec in myocardium, liver, and spleen 24 h post ischemia. In the infarcted area, the PBMCsec mainly induced genes that were essential for cardiomyocyte function and simultaneously downregulated pro-inflammatory genes. Interestingly, genes associated with pro-inflammatory processes were activated in the transition zone, while being downregulated in the remote zone. In the liver, we observed a pronounced inhibition of immune responses using the PBMCsec, while genes involved in urea and tricarboxylic cycles were induced. The spleen displayed elevated lipid metabolism and reduced immunological processes. Together, our study suggested several types of pharmacodynamics by which the PBMCsec conferred immediate cardioprotection. Furthermore, our data supported the assumption that an AMI significantly affects distal organs, suggesting that a holistic treatment of an AMI, as achieved by PBMCsec, might be highly beneficial.<\/jats:p>","DOI":"10.3390\/biology11010116","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T10:57:37Z","timestamp":1642071457000},"page":"116","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Secretome of Stressed Peripheral Blood Mononuclear Cells Alters Transcriptome Signature in Heart, Liver, and Spleen after an Experimental Acute Myocardial Infarction: An In Silico Analysis"],"prefix":"10.3390","volume":"11","author":[{"given":"Caterina Selina","family":"Mildner","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Applied Immunology Laboratory, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Aposcience AG, 1200 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1005-2985","authenticated-orcid":false,"given":"Dragan","family":"Copic","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Applied Immunology Laboratory, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Aposcience AG, 1200 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4610-7853","authenticated-orcid":false,"given":"Matthias","family":"Zimmermann","sequence":"additional","affiliation":[{"name":"Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Department of Oral and Maxillofacial Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Lichtenauer","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine II, Division of Cardiology, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Direder","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Applied Immunology Laboratory, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Aposcience AG, 1200 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katharina","family":"Klas","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Applied Immunology Laboratory, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Aposcience AG, 1200 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Bormann","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Applied Immunology Laboratory, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Aposcience AG, 1200 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5178-9967","authenticated-orcid":false,"given":"Alfred","family":"Gugerell","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Applied Immunology Laboratory, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Aposcience AG, 1200 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6037-5475","authenticated-orcid":false,"given":"Bernhard","family":"Moser","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konrad","family":"Hoetzenecker","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4388-7580","authenticated-orcid":false,"given":"Lucian","family":"Beer","sequence":"additional","affiliation":[{"name":"Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7083-2107","authenticated-orcid":false,"given":"Mariann","family":"Gy\u00f6ngy\u00f6si","sequence":"additional","affiliation":[{"name":"Department of Medicine II, Division of Cardiology, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hendrik Jan","family":"Ankersmit","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Applied Immunology Laboratory, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Aposcience AG, 1200 Vienna, Austria"},{"name":"Christian Doppler Laboratory for Cardiac and Thoracic Diagnosis and Regeneration, Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Laggner","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Applied Immunology Laboratory, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Aposcience AG, 1200 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,13]]},"reference":[{"key":"ref_1","unstructured":"(2021, September 23). World Health Organization. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/the-top-10-causes-of-death."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e005375","DOI":"10.1161\/CIRCOUTCOMES.118.005375","article-title":"Mortality From Ischemic Heart Disease","volume":"12","author":"Nowbar","year":"2019","journal-title":"Circ. Cardiovasc. Qual. Outcomes"},{"key":"ref_3","unstructured":"(2010). Cardiovascular Disability: Updating the Social Security Listings, National Academies Press."},{"key":"ref_4","unstructured":"Mechanic, O.J., Gavin, M., Grossman, S.A., and Ziegler, K. (2021). Acute Myocardial Infarction (Nursing), StatPearls."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1080\/1061186X.2020.1725769","article-title":"Molecular imaging of myocardial necrosis: An updated mini-review","volume":"28","author":"Zhang","year":"2020","journal-title":"J. Drug Target"},{"key":"ref_6","doi-asserted-by":"crossref","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":"ref_7","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1172\/JCI115999","article-title":"Neutrophil induced oxidative injury of cardiac myocytes. A compartmented system requiring CD11b\/CD18-ICAM-1 adherence","volume":"90","author":"Entman","year":"1992","journal-title":"J. Clin. Investig."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e2346","DOI":"10.1212\/WNL.0000000000009532","article-title":"Thrombus NET content is associated with clinical outcome in stroke and myocardial infarction","volume":"94","author":"Novotny","year":"2020","journal-title":"Neurology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1161\/CIRCRESAHA.116.304944","article-title":"Coronary neutrophil extracellular trap burden and deoxyribonuclease activity in ST-elevation acute coronary syndrome are predictors of ST-segment resolution and infarct size","volume":"116","author":"Mangold","year":"2015","journal-title":"Circ. Res."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Mangold, A., Ondracek, A.S., Hofbauer, T.M., Scherz, T., Artner, T., Panagiotides, N., Beitzke, D., Ruzicka, G., Nistler, S., and Wohlschlager-Krenn, E. (2021). Culprit site extracellular DNA and microvascular obstruction in ST-elevation myocardial infarction. Cardiovasc. Res.","DOI":"10.1093\/cvr\/cvab217"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"43958","DOI":"10.1038\/srep43958","article-title":"Sequential activation of different pathway networks in ischemia-affected and non-affected myocardium, inducing intrinsic remote conditioning to prevent left ventricular remodeling","volume":"7","author":"Pavo","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"60809","DOI":"10.18632\/oncotarget.17955","article-title":"Analysis of region specific gene expression patterns in the heart and systemic responses after experimental myocardial ischemia","volume":"8","author":"Zimmermann","year":"2017","journal-title":"Oncotarget"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/S1010-7940(03)00325-7","article-title":"Mobilization and homing of bone marrow stromal cells in myocardial infarction","volume":"24","author":"Bittira","year":"2003","journal-title":"Eur. J. Cardiothorac. Surg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4552","DOI":"10.7150\/thno.24723","article-title":"Liver-heart crosstalk controls IL-22 activity in cardiac protection after myocardial infarction","volume":"8","author":"Tang","year":"2018","journal-title":"Theranostics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s00011-013-0605-4","article-title":"Myocardial infarction causes inflammation and leukocyte recruitment at remote sites in the myocardium and in the renal glomerulus","volume":"62","author":"Ruparelia","year":"2013","journal-title":"Inflamm. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1093\/eurheartj\/eht331","article-title":"Monocyte subset accumulation in the human heart following acute myocardial infarction and the role of the spleen as monocyte reservoir","volume":"35","author":"Delewi","year":"2014","journal-title":"Eur. Heart J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1111\/j.1365-2362.2009.02111.x","article-title":"Irradiated cultured apoptotic peripheral blood mononuclear cells regenerate infarcted myocardium","volume":"39","author":"Ankersmit","year":"2009","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1007\/s00395-011-0173-0","article-title":"Intravenous and intramyocardial injection of apoptotic white blood cell suspensions prevents ventricular remodelling by increasing elastin expression in cardiac scar tissue after myocardial infarction","volume":"106","author":"Lichtenauer","year":"2011","journal-title":"Basic Res. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1038\/s41419-019-1974-6","article-title":"Tissue-regenerative potential of the secretome of gamma-irradiated peripheral blood mononuclear cells is mediated via TNFRSF1B-induced necroptosis","volume":"10","author":"Simader","year":"2019","journal-title":"Cell Death. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"16662","DOI":"10.1038\/srep16662","article-title":"Analysis of the Secretome of Apoptotic Peripheral Blood Mononuclear Cells: Impact of Released Proteins and Exosomes for Tissue Regeneration","volume":"5","author":"Beer","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"102774","DOI":"10.1016\/j.ebiom.2020.102774","article-title":"Therapeutic potential of lipids obtained from gamma-irradiated PBMCs in dendritic cell-mediated skin inflammation","volume":"55","author":"Laggner","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1283","DOI":"10.1007\/s00395-011-0224-6","article-title":"Secretome of apoptotic peripheral blood cells (APOSEC) confers cytoprotection to cardiomyocytes and inhibits tissue remodelling after acute myocardial infarction: A preclinical study","volume":"106","author":"Lichtenauer","year":"2011","journal-title":"Basic Res. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Panahipour, L., Kochergina, E., Laggner, M., Zimmermann, M., Mildner, M., Ankersmit, H.J., and Gruber, R. (2020). Role for Lipids Secreted by Irradiated Peripheral Blood Mononuclear Cells in Inflammatory Resolution in Vitro. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134694"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"18016","DOI":"10.1038\/s41598-018-36928-6","article-title":"Different pro-angiogenic potential of gamma-irradiated PBMC-derived secretome and its subfractions","volume":"8","author":"Wagner","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Panahipour, L., Kargarpour, Z., Laggner, M., Mildner, M., Ankersmit, H.J., and Gruber, R. (2020). TGF-beta in the Secretome of Irradiated Peripheral Blood Mononuclear Cells Supports In Vitro Osteoclastogenesis. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228569"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1111\/eci.12667","article-title":"Dying blood mononuclear cell secretome exerts antimicrobial activity","volume":"46","author":"Kasiri","year":"2016","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1007\/s00395-012-0292-2","article-title":"Secretome of apoptotic peripheral blood cells (APOSEC) attenuates microvascular obstruction in a porcine closed chest reperfused acute myocardial infarction model: Role of platelet aggregation and vasodilation","volume":"107","author":"Hoetzenecker","year":"2012","journal-title":"Basic Res. Cardiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e10186","DOI":"10.1002\/btm2.10186","article-title":"The secretome of stressed peripheral blood mononuclear cells increases tissue survival in a rodent epigastric flap model","volume":"6","author":"Hacker","year":"2021","journal-title":"Bioeng. Transl. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.omtm.2020.06.008","article-title":"Quantitative Hybrid Cardiac [(18)F]FDG-PET-MRI Images for Assessment of Cardiac Repair by Preconditioned Cardiosphere-Derived Cells","volume":"18","author":"Winkler","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3541","DOI":"10.1016\/j.biomaterials.2013.12.071","article-title":"Long-acting beneficial effect of percutaneously intramyocardially delivered secretome of apoptotic peripheral blood cells on porcine chronic ischemic left ventricular dysfunction","volume":"35","author":"Pavo","year":"2014","journal-title":"Biomaterials"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"131","DOI":"10.12688\/f1000research.4219.2","article-title":"Secretomes of apoptotic mononuclear cells ameliorate neurological damage in rats with focal ischemia","volume":"3","author":"Altmann","year":"2014","journal-title":"F1000Res"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1093\/eurheartj\/ehs459","article-title":"Mononuclear cell secretome protects from experimental autoimmune myocarditis","volume":"36","author":"Hoetzenecker","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.expneurol.2015.03.013","article-title":"The secretome of apoptotic human peripheral blood mononuclear cells attenuates secondary damage following spinal cord injury in rats","volume":"267","author":"Haider","year":"2015","journal-title":"Exp. Neurol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"25168","DOI":"10.1038\/srep25168","article-title":"Paracrine Factors from Irradiated Peripheral Blood Mononuclear Cells Improve Skin Regeneration and Angiogenesis in a Porcine Burn Model","volume":"6","author":"Hacker","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5598","DOI":"10.1038\/s41598-019-42057-5","article-title":"Toxicological testing of allogeneic secretome derived from peripheral mononuclear cells (APOSEC): A novel cell-free therapeutic agent in skin disease","volume":"9","author":"Wuschko","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6216","DOI":"10.1038\/s41598-017-06223-x","article-title":"Safety and tolerability of topically administered autologous, apoptotic PBMC secretome (APOSEC) in dermal wounds: A randomized Phase 1 trial (MARSYAS I)","volume":"7","author":"Simader","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13063-020-04948-1","article-title":"Safety and clinical efficacy of the secretome of stressed peripheral blood mononuclear cells in patients with diabetic foot ulcer-study protocol of the randomized, placebo-controlled, double-blind, multicenter, international phase II clinical trial MARSYAS II","volume":"22","author":"Gugerell","year":"2021","journal-title":"Trials"},{"key":"ref_38","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_39","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/bioinformatics\/btp101","article-title":"ClueGO: A Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks","volume":"25","author":"Bindea","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_40","first-page":"100141","article-title":"clusterProfiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation"},{"key":"ref_41","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_42","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1182\/blood-2013-07-514992","article-title":"VWF-mediated leukocyte recruitment with chromatin decondensation by PAD4 increases myocardial ischemia\/reperfusion injury in mice","volume":"123","author":"Savchenko","year":"2014","journal-title":"Blood"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.cardiores.2007.03.027","article-title":"S100A4 is upregulated in injured myocardium and promotes growth and survival of cardiac myocytes","volume":"75","author":"Schneider","year":"2007","journal-title":"Cardiovasc. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.trsl.2015.07.002","article-title":"Inflammation as a therapeutic target in myocardial infarction: Learning from past failures to meet future challenges","volume":"167","author":"Saxena","year":"2016","journal-title":"Transl. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1161\/01.CIR.67.5.1016","article-title":"Reduction of the extent of ischemic myocardial injury by neutrophil depletion in the dog","volume":"67","author":"Romson","year":"1983","journal-title":"Circulation"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/j.ahj.2008.07.008","article-title":"Uncontrolled immune response in acute myocardial infarction: Unraveling the thread","volume":"156","author":"Bodi","year":"2008","journal-title":"Am. Heart J."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/S0735-1097(02)02136-8","article-title":"The effect of blockade of the CD11\/CD18 integrin receptor on infarct size in patients with acute myocardial infarction treated with direct angioplasty: The results of the HALT-MI study","volume":"40","author":"Faxon","year":"2002","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1161\/01.CIR.57.1.56","article-title":"Mummification of the infarcted myocardium by high dose corticosteroids","volume":"57","author":"Kloner","year":"1978","journal-title":"Circulation"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1172\/JCI11273","article-title":"Pressure-independent enhancement of cardiac hypertrophy in natriuretic peptide receptor A-deficient mice","volume":"107","author":"Knowles","year":"2001","journal-title":"J. Clin. Invest."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"10736","DOI":"10.1111\/jcmm.17015","article-title":"Identification of MYH6 as the potential gene for human ischaemic cardiomyopathy","volume":"25","author":"Chen","year":"2021","journal-title":"J. Cell. Mol. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1093\/eurheartj\/ehm048","article-title":"Evaluation of cardiac sympathetic nerve activity and left ventricular remodelling in patients with dilated cardiomyopathy on the treatment containing carvedilol","volume":"28","author":"Kasama","year":"2007","journal-title":"Eur. Heart J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1016\/S0140-6736(07)61634-1","article-title":"Human atrial natriuretic peptide and nicorandil as adjuncts to reperfusion treatment for acute myocardial infarction (J-WIND): Two randomised trials","volume":"370","author":"Kitakaze","year":"2007","journal-title":"Lancet"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.yjmcc.2016.12.002","article-title":"Cardiac inflammation in genetic dilated cardiomyopathy caused by MYBPC3 mutation","volume":"102","author":"Lynch","year":"2017","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1007\/s00395-014-0414-0","article-title":"Hypoxic preconditioning protects rat hearts against ischemia-reperfusion injury via the arachidonate12-lipoxygenase\/transient receptor potential vanilloid 1 pathway","volume":"109","author":"Lu","year":"2014","journal-title":"Basic Res. Cardiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1016\/j.cmet.2021.08.014","article-title":"Pharmacological inhibition of arachidonate 12-lipoxygenase ameliorates myocardial ischemia-reperfusion injury in multiple species","volume":"33","author":"Zhang","year":"2021","journal-title":"Cell. Metab."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1038\/nm.4451","article-title":"An ALOX12-12-HETE-GPR31 signaling axis is a key mediator of hepatic ischemia-reperfusion injury","volume":"24","author":"Zhang","year":"2018","journal-title":"Nat. Med."},{"key":"ref_57","first-page":"84","article-title":"Comparative study of gene expression profiles rooted in acute myocardial infarction and ischemic\/reperfusion rat models","volume":"10","author":"Wang","year":"2020","journal-title":"Am. J. Cardiovasc. Dis."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"H190","DOI":"10.1152\/ajpheart.00243.2016","article-title":"MMP-9 signaling in the left ventricle following myocardial infarction","volume":"311","author":"Iyer","year":"2016","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s12265-020-10006-7","article-title":"Chemokines in Myocardial Infarction","volume":"14","author":"Chen","year":"2021","journal-title":"J. Cardiovasc. Transl. Res."},{"key":"ref_60","doi-asserted-by":"crossref","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":"ref_61","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.yjmcc.2013.11.015","article-title":"Fibroblasts in myocardial infarction: A role in inflammation and repair","volume":"70","author":"Shinde","year":"2014","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_62","first-page":"25","article-title":"The Speed of Healing of Myocardial Infarction: A Study of the Pathologic Anatomy in Seventy-Two Cases","volume":"18","author":"Mallory","year":"1939","journal-title":"Am. Heart J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1002\/ags3.12058","article-title":"Changes of liver metabolites following hepatectomy with ischemia reperfusion towards liver regeneration","volume":"2","author":"Saito","year":"2018","journal-title":"Ann. Gastroenterol. Surg."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.ijcard.2011.07.103","article-title":"Ganoderma lucidum ameliorate mitochondrial damage in isoproterenol-induced myocardial infarction in rats by enhancing the activities of TCA cycle enzymes and respiratory chain complexes","volume":"165","author":"Sudheesh","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1161\/CIRCIMAGING.113.001093","article-title":"Metabolic activity of the spleen and bone marrow in patients with acute myocardial infarction evaluated by 18f-fluorodeoxyglucose positron emission tomograpic imaging","volume":"7","author":"Kim","year":"2014","journal-title":"Circ. Cardiovasc. Imaging"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.yjmcc.2015.04.003","article-title":"Resolvin D1 activates the inflammation resolving response at splenic and ventricular site following myocardial infarction leading to improved ventricular function","volume":"84","author":"Kain","year":"2015","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1080\/078538902321012414","article-title":"Apoptosis in myocardial infarction","volume":"34","author":"Rodriguez","year":"2002","journal-title":"Ann. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.bbrc.2004.10.064","article-title":"Temporal and spatial characteristics of apoptosis in the infarcted rat heart","volume":"325","author":"Zhao","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_69","first-page":"100558","article-title":"Association of comorbidities with clinical outcomes in patients after acute myocardial infarction","volume":"29","author":"Baechli","year":"2020","journal-title":"Int. J. Cardiol. Heart Vasc."}],"container-title":["Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-7737\/11\/1\/116\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:27:33Z","timestamp":1760362053000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-7737\/11\/1\/116"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,13]]},"references-count":69,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["biology11010116"],"URL":"https:\/\/doi.org\/10.3390\/biology11010116","relation":{},"ISSN":["2079-7737"],"issn-type":[{"type":"electronic","value":"2079-7737"}],"subject":[],"published":{"date-parts":[[2022,1,13]]}}}