{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T06:08:34Z","timestamp":1780985314436,"version":"3.54.1"},"reference-count":36,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T00:00:00Z","timestamp":1637625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Economy and Competitiveness-MICINN","award":["SAF2017-84324-C2-1-R; PID2019-110137RB-I00"],"award-info":[{"award-number":["SAF2017-84324-C2-1-R; PID2019-110137RB-I00"]}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI17\/01487, PIC18\/00014, ICI19\/00039, PI18\/00256, PI18\/01227, ICI20\/00135"],"award-info":[{"award-number":["PI17\/01487, PIC18\/00014, ICI19\/00039, PI18\/00256, PI18\/01227, ICI20\/00135"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Red de Terapia Celular-TerCel","award":["RD16\/0011\/0006"],"award-info":[{"award-number":["RD16\/0011\/0006"]}]},{"name":"Centro de Investigaci\u00f3n en Red en Enfermedades Cardiovasculares","award":["CB16\/11\/00403"],"award-info":[{"award-number":["CB16\/11\/00403"]}]},{"DOI":"10.13039\/501100003030","name":"Ag\u00e8ncia de Gesti\u00f3 d'Ajuts Universitaris i de Recerca","doi-asserted-by":"publisher","award":["2017-SGR-483, 2019PROD00122"],"award-info":[{"award-number":["2017-SGR-483, 2019PROD00122"]}],"id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010434","name":"Fundaci\u00f3n Bancaria Caixa d\u2019Estalvis i Pensions de Barcelona","doi-asserted-by":"publisher","award":["HR17-00627, CI20-00230"],"award-info":[{"award-number":["HR17-00627, CI20-00230"]}],"id":[{"id":"10.13039\/100010434","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Specific proteins and processes have been identified in post-myocardial infarction (MI) pathological remodeling, but a comprehensive understanding of the complete molecular evolution is lacking. We generated microarray data from swine heart biopsies at baseline and 6, 30, and 45 days after infarction to feed machine-learning algorithms. We cross-validated the results using available clinical and experimental information. MI progression was accompanied by the regulation of adipogenesis, fatty acid metabolism, and epithelial\u2013mesenchymal transition. The infarct core region was enriched in processes related to muscle contraction and membrane depolarization. Angiogenesis was among the first morphogenic responses detected as being sustained over time, but other processes suggesting post-ischemic recapitulation of embryogenic processes were also observed. Finally, protein-triggering analysis established the key genes mediating each process at each time point, as well as the complete adverse remodeling response. We modeled the behaviors of these genes, generating a description of the integrative mechanism of action for MI progression. This mechanistic analysis overlapped at different time points; the common pathways between the source proteins and cardiac remodeling involved IGF1R, RAF1, KPCA, JUN, and PTN11 as modulators. Thus, our data delineate a structured and comprehensive picture of the molecular remodeling process, identify new potential biomarkers or therapeutic targets, and establish therapeutic windows during disease progression.<\/jats:p>","DOI":"10.3390\/cells10123268","type":"journal-article","created":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T02:46:08Z","timestamp":1637721968000},"page":"3268","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Deep Learning Analyses to Delineate the Molecular Remodeling Process after Myocardial Infarction"],"prefix":"10.3390","volume":"10","author":[{"given":"Oriol","family":"Iborra-Egea","sequence":"first","affiliation":[{"name":"ICREC Research Program, Health Sciences Research Institute Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona, 08916 Barcelona, 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Health Sciences Research Institute Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona, 08916 Barcelona, Spain"},{"name":"CIBERCV, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Ferrer-Curriu","sequence":"additional","affiliation":[{"name":"ICREC Research Program, Health Sciences Research Institute Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona, 08916 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8215-872X","authenticated-orcid":false,"given":"Cristina","family":"Seg\u00fa-Verg\u00e9s","sequence":"additional","affiliation":[{"name":"Anaxomics Biotech S.L., Diputaci\u00f3 237 1r 1a, 08007 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Araceli","family":"Mellado-Bergillos","sequence":"additional","affiliation":[{"name":"ICREC Research Program, Health Sciences Research Institute Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona, 08916 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pol","family":"Gomez-Puchades","sequence":"additional","affiliation":[{"name":"ICREC Research Program, Health Sciences Research Institute Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona, 08916 Barcelona, Spain"},{"name":"CIBERCV, Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paloma","family":"Gastelurrutia","sequence":"additional","affiliation":[{"name":"ICREC Research Program, Health Sciences Research Institute Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona, 08916 Barcelona, Spain"},{"name":"CIBERCV, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Institut d\u2019Investigaci\u00f3 Biom\u00e8dica de Bellvitge-IDIBELL, 08007 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoni","family":"Bayes-Genis","sequence":"additional","affiliation":[{"name":"ICREC Research Program, Health Sciences Research Institute Germans Trias i Pujol, Universitat Aut\u00f2noma de Barcelona, 08916 Barcelona, Spain"},{"name":"CIBERCV, Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Cardiology Service, Germans Trias i Pujol University Hospital, 08916 Badalona, Spain"},{"name":"Department of Medicine, Autonomous University of Barcelona, 08916 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1378\/chest.73.6.843","article-title":"The Histopathologic Evolution of Myocardial Infarction","volume":"73","author":"Fishbein","year":"1978","journal-title":"Chest"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1016\/j.jacc.2019.02.018","article-title":"Type 2 Myocardial Infarction: JACC Review Topic of the Week","volume":"73","author":"Sandoval","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1161\/CIRCRESAHA.119.315101","article-title":"Myocardial Infarction as a Clinical End Point in Research","volume":"124","author":"DeFilippis","year":"2019","journal-title":"Circ. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1215802","DOI":"10.1155\/2020\/1215802","article-title":"Adverse Cardiac Remodelling after Acute Myocardial Infarction: Old and New Biomarkers","volume":"2020","author":"Berezin","year":"2020","journal-title":"Dis. Markers"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1002\/ehf2.12618","article-title":"Left ventricular remodelling after ST-segment elevation myocardial infarction: Sex differences and prognosis","volume":"7","author":"Abou","year":"2020","journal-title":"ESC Heart Fail."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1161\/01.CIR.81.4.1161","article-title":"Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications","volume":"81","author":"Pfeffer","year":"1990","journal-title":"Circulation"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2981","DOI":"10.1161\/01.CIR.101.25.2981","article-title":"Left Ventricular Remodeling After Myocardial Infarction","volume":"101","author":"Sutton","year":"2000","journal-title":"Circulation"},{"key":"ref_8","first-page":"222","article-title":"Heart failure after myocardial infarction: Incidence and predictors","volume":"8","author":"Stehlik","year":"2020","journal-title":"ESC Heart Fail."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1038\/nature06798","article-title":"Tackling heart failure in the twenty-first century","volume":"451","author":"Mudd","year":"2008","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1161\/01.RES.86.9.939","article-title":"Altered Patterns of Gene Expression in Response to Myocardial Infarction","volume":"86","author":"Stanton","year":"2000","journal-title":"Circ. Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1007\/s00335-005-0120-1","article-title":"Earliest changes in the left ventricular transcriptome post-myocardial infarction","volume":"17","author":"Harpster","year":"2006","journal-title":"Mamm. Genome"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1007\/s00109-008-0385-4","article-title":"Sex-specific pathways in early cardiac response to pressure overload in mice","volume":"86","author":"Witt","year":"2008","journal-title":"J. Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.tig.2010.05.001","article-title":"From \u2018differential expression\u2019 to \u2018differential networking\u2019\u2014Identification of dysfunctional regulatory networks in diseases","volume":"26","year":"2010","journal-title":"Trends Genet."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1831","DOI":"10.1161\/CIRCULATIONAHA.119.044557","article-title":"Single-Cell RNA-seq Analysis Reveals a Crucial Role for Collagen Triple Helix Repeat Containing 1 (CTHRC1) Cardiac Fibroblasts after Myocardial Infarction","volume":"142","author":"Romero","year":"2020","journal-title":"Circulation"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.cell.2019.05.010","article-title":"The Translational Landscape of the Human Heart","volume":"178","author":"Witte","year":"2019","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"91","DOI":"10.3389\/fcvm.2019.00091","article-title":"Relevance of Multi-Omics Studies in Cardiovascular Diseases","volume":"6","author":"Wang","year":"2019","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Prat-Vidal, C., G\u00e1lvez-Mont\u00f3n, C., Nonell, L., Puigdecanet, E., Astier, L., Sol\u00e9, F., and Bayes-Genis, A. (2013). Identification of Temporal and Region-Specific Myocardial Gene Expression Patterns in Response to Infarction in Swine. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0054785"},{"key":"ref_18","unstructured":"Anaxomics Biotech SL (2019, February 08). TPMS Technology. Available online: http:\/\/www.anaxomics.com\/ourtechnology\/tpms\/#tpms."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1093\/cvr\/cvr136","article-title":"Transposition of a pericardial-derived vascular adipose flap for myocardial salvage after infarct","volume":"91","author":"Roura","year":"2011","journal-title":"Cardiovasc. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1093\/biostatistics\/4.2.249","article-title":"Exploration, normalization, and summaries of high density oligonucleotide array probe level data","volume":"4","author":"Irizarry","year":"2003","journal-title":"Biostatistics"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"D234","DOI":"10.1093\/nar\/gku1203","article-title":"InParanoid 8: Orthology analysis between 273 proteomes, mostly eukaryotic","volume":"43","author":"Sonnhammer","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"883","DOI":"10.15252\/msb.20167144","article-title":"Gene-specific correlation of RNA and protein levels in human cells and tissues","volume":"12","author":"Edfors","year":"2016","journal-title":"Mol. Syst. Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical And Powerful Approach To Multiple Testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B Methodol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.2307\/2532694","article-title":"Adjusted P-Values for Simultaneous Inference","volume":"48","author":"Wright","year":"1992","journal-title":"Biometrics"},{"key":"ref_25","unstructured":"Bishop, C.M. (2006). Pattern Recognition and Machine Learning, Springer. [1st ed.]."},{"key":"ref_26","first-page":"278","article-title":"Methods and approaches in the topology-based analysis of biological pathways","volume":"4","author":"Emitrea","year":"2013","journal-title":"Front. Physiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1038\/ng1180","article-title":"PGC-1\u03b1-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes","volume":"34","author":"Mootha","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.chom.2015.11.002","article-title":"Meta- and Orthogonal Integration of Influenza \u201cOMICs\u201d Data Defines a Role for UBR4 in Virus Budding","volume":"18","author":"Tripathi","year":"2015","journal-title":"Cell Host Microbe"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/nmeth.3901","article-title":"The Perseus computational platform for comprehensive analysis of (prote)omics data","volume":"13","author":"Tyanova","year":"2016","journal-title":"Nat. Methods"},{"key":"ref_31","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_32","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1093\/cvr\/cvz057","article-title":"Toll-like receptor 7 deficiency promotes survival and reduces adverse left ventricular remodelling after myocardial infarction","volume":"115","author":"Chong","year":"2019","journal-title":"Cardiovasc. Res."},{"key":"ref_33","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_34","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.ddmec.2007.12.006","article-title":"Mechanisms of postinfarct left ventricular remodeling","volume":"4","author":"French","year":"2007","journal-title":"Drug Discov. Today Dis. Mech."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.2174\/13816128113199990449","article-title":"Targeting the chemokines in cardiac repair","volume":"20","author":"Cavalera","year":"2014","journal-title":"Curr. Pharm. Des."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1038\/d41586-019-00681-1","article-title":"Matrix mimics shape cell studies","volume":"566","author":"Madhusoodanan","year":"2019","journal-title":"Nature"}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/12\/3268\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:34:30Z","timestamp":1760168070000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/12\/3268"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,23]]},"references-count":36,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["cells10123268"],"URL":"https:\/\/doi.org\/10.3390\/cells10123268","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,23]]}}}