{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T05:55:57Z","timestamp":1764050157258,"version":"3.45.0"},"reference-count":74,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T00:00:00Z","timestamp":1763769600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Some studies report better outcomes in cell therapy for myocardial infarction (MI) with repeated administrations. We aimed to elucidate the potential differences in terms of cardiac function and protein expression after one or three doses of cardiosphere-derived cells (CDCs) in a porcine MI model. CDCs were isolated from swine cardiac explants, cultured in cardiomyocyte growth medium (CGM), and prepared for administration. Pigs surviving a 90 min balloon occlusion of the mid-left anterior descending coronary artery (LAD) were randomly allocated to receive vehicle (CON), one (D1), or three (D3) doses of 30 \u00d7 106 CDCs via the infarct-related coronary artery. Cardiac function was assessed with magnetic resonance at baseline and 10 weeks. Programmed electrical stimulation to study arrhythmogenicity was performed at 10 weeks. High-throughput quantitative proteomic analysis of infarcted tissue was performed to identify biological processes based on protein abundance changes between groups. No significant differences were found between the three groups for any cardiac function parameter at 10 weeks. No increase in ventricular tachycardia inducibility was seen in treated groups. However, gene ontology and topological analyses revealed potentially beneficial molecular adaptations. Upregulation of GYS1, AGL, and GBE1 indicated an increase in glycogen biosynthesis and energy availability, while an increase in ANK2, along with hub proteins ALB and TRAP1, suggested cardioprotective effects. Furthermore, the increase in remodeling-related proteins, including EPHA4, PODN, and ALPK3, pointed to favorable structural adaptation following infarction. In conclusion, the intracoronary administration of single or repeated doses of 30 \u00d7 106 CDCs to a porcine reperfused MI model shows only slight differential improvement in both cardiac function and protein profile in this experimental setting, thus presenting limited translational potential.<\/jats:p>","DOI":"10.3390\/ijms262311294","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T09:02:07Z","timestamp":1763974927000},"page":"11294","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Administration of Single or Repeated Doses of CDCs in a Swine Model of Reperfused Myocardial Infarction: Magnetic Resonance and Proteomics Evaluation"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8989-2468","authenticated-orcid":false,"given":"Mar\u00eda \u00c1ngeles","family":"de Pedro","sequence":"first","affiliation":[{"name":"Centro de Cirug\u00eda de M\u00ednima Invasi\u00f3n Jes\u00fas Us\u00f3n, 10071 C\u00e1ceres, Spain"},{"name":"Red Espa\u00f1ola de Terapias Avanzadas RICORS-TERAV, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9031-2929","authenticated-orcid":false,"given":"Claudia","family":"B\u00e1ez-D\u00edaz","sequence":"additional","affiliation":[{"name":"Centro de Cirug\u00eda de M\u00ednima Invasi\u00f3n Jes\u00fas Us\u00f3n, 10071 C\u00e1ceres, Spain"},{"name":"Red Espa\u00f1ola de Terapias Avanzadas RICORS-TERAV, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8645-9477","authenticated-orcid":false,"given":"Inmaculada","family":"Jorge","sequence":"additional","affiliation":[{"name":"Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain"},{"name":"CIBER de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5735-2985","authenticated-orcid":false,"given":"F\u00e1tima","family":"V\u00e1zquez-Lopez","sequence":"additional","affiliation":[{"name":"Centro de Cirug\u00eda de M\u00ednima Invasi\u00f3n Jes\u00fas Us\u00f3n, 10071 C\u00e1ceres, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1841-9183","authenticated-orcid":false,"given":"Axiel","family":"Torrescusa-Bermejo","sequence":"additional","affiliation":[{"name":"Centro de Cirug\u00eda de M\u00ednima Invasi\u00f3n Jes\u00fas Us\u00f3n, 10071 C\u00e1ceres, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beatriz","family":"Martinez-Fernandez","sequence":"additional","affiliation":[{"name":"Micros Veterinaria, 24007 Le\u00f3n, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9126-7047","authenticated-orcid":false,"given":"Mar\u00eda","family":"Pulido","sequence":"additional","affiliation":[{"name":"Centro de Cirug\u00eda de M\u00ednima Invasi\u00f3n Jes\u00fas Us\u00f3n, 10071 C\u00e1ceres, Spain"},{"name":"Red Espa\u00f1ola de Terapias Avanzadas RICORS-TERAV, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5051-5913","authenticated-orcid":false,"given":"Esther","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Centro de Cirug\u00eda de M\u00ednima Invasi\u00f3n Jes\u00fas Us\u00f3n, 10071 C\u00e1ceres, Spain"},{"name":"Red Espa\u00f1ola de Terapias Avanzadas RICORS-TERAV, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1461-5092","authenticated-orcid":false,"given":"Jes\u00fas","family":"V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Centro Nacional de Investigaciones Cardiovasculares, 28029 Madrid, Spain"},{"name":"CIBER de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2138-988X","authenticated-orcid":false,"given":"Francisco M.","family":"S\u00e1nchez-Margallo","sequence":"additional","affiliation":[{"name":"Centro de Cirug\u00eda de M\u00ednima Invasi\u00f3n Jes\u00fas Us\u00f3n, 10071 C\u00e1ceres, Spain"},{"name":"Red Espa\u00f1ola de Terapias Avanzadas RICORS-TERAV, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1740-7029","authenticated-orcid":false,"given":"Veronica","family":"Crisostomo","sequence":"additional","affiliation":[{"name":"Centro de Cirug\u00eda de M\u00ednima Invasi\u00f3n Jes\u00fas Us\u00f3n, 10071 C\u00e1ceres, Spain"},{"name":"Red Espa\u00f1ola de Terapias Avanzadas RICORS-TERAV, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1161\/CIRCRESAHA.117.311302","article-title":"Meta-Analysis of Cell Therapy Studies in Heart Failure and Acute Myocardial Infarction","volume":"123","author":"Gyongyosi","year":"2018","journal-title":"Circ. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1161\/CIRCRESAHA.117.311565","article-title":"Translational Research in Cardiovascular Repair","volume":"122","author":"Chamuleau","year":"2018","journal-title":"Circ. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1161\/CIRCRESAHA.117.310710","article-title":"Repeated Cell Therapy: A Paradigm Shift Whose Time Has Come","volume":"120","author":"Bolli","year":"2017","journal-title":"Circ. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1093\/cvr\/cvae173","article-title":"Intravenous infusions of mesenchymal stromal cells have cumulative beneficial effects in a porcine model of chronic ischaemic cardiomyopathy","volume":"120","author":"Tang","year":"2024","journal-title":"Cardiovasc. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e007400","DOI":"10.1161\/JAHA.117.007400","article-title":"Repeated Administrations of Cardiac Progenitor Cells Are Superior to a Single Administration of an Equivalent Cumulative Dose","volume":"7","author":"Tang","year":"2018","journal-title":"J. Am. Heart Assoc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1161\/CIRCRESAHA.118.313251","article-title":"New Paradigms in Cell Therapy: Repeated Dosing, Intravenous Delivery, Immunomodulatory Actions, and New Cell Types","volume":"123","author":"Wysoczynski","year":"2018","journal-title":"Circ. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1161\/CIRCRESAHA.116.308937","article-title":"Repeated Administrations of Cardiac Progenitor Cells Are Markedly More Effective Than a Single Administration","volume":"119","author":"Tokita","year":"2016","journal-title":"Circ. Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.jcyt.2013.07.016","article-title":"Incremental benefits of repeated mesenchymal stromal cell administration compared with solitary intervention after myocardial infarction","volume":"16","author":"Richardson","year":"2014","journal-title":"Cytotherapy"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/s00395-017-0606-5","article-title":"Repeated doses of cardiac mesenchymal cells are therapeutically superior to a single dose in mice with old myocardial infarction","volume":"112","author":"Guo","year":"2017","journal-title":"Basic Res. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.ijcard.2006.04.092","article-title":"Repeated direct endomyocardial transplantation of allogeneic mesenchymal stem cells: Safety of a high dose, \u201coff-the-shelf\u201d, cellular cardiomyoplasty strategy","volume":"117","author":"Poh","year":"2007","journal-title":"Int. J. Cardiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s00395-019-0718-1","article-title":"Repeated cell transplantation and adjunct renal denervation in ischemic heart failure: Exploring modalities for improving cell therapy efficacy","volume":"114","author":"Polhemus","year":"2019","journal-title":"Basic Res. Cardiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1002\/sctm.19-0013","article-title":"Optimization of Timing and Times for Administration of Atorvastatin-Pretreated Mesenchymal Stem Cells in a Preclinical Model of Acute Myocardial Infarction","volume":"8","author":"Xu","year":"2019","journal-title":"Stem Cells Transl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Li, Q., Guo, Y., Nong, Y., Tomlin, A., Gumpert, A., Zhu, X., Hassan, S.A., and Bolli, R. (2021). Comparison of Repeated Doses of C-kit-Positive Cardiac Cells versus a Single Equivalent Combined Dose in a Murine Model of Chronic Ischemic Cardiomyopathy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063145"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1016\/j.healun.2016.05.008","article-title":"Repeated transplantation of allogeneic cardiosphere-derived cells boosts therapeutic benefits without immune sensitization in a rat model of myocardial infarction","volume":"35","author":"Reich","year":"2016","journal-title":"J. Heart Lung Transplant."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1007\/s12015-020-10063-0","article-title":"Comparison of One and Three Intraventricular Injections of Cardiac Progenitor Cells in a Murine Model of Chronic Ischemic Cardiomyopathy","volume":"17","author":"Guo","year":"2021","journal-title":"Stem Cell Rev. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1186\/s13287-023-03495-1","article-title":"Effect of once versus twice intracoronary injection of allogeneic-derived mesenchymal stromal cells after acute myocardial infarction: BOOSTER-TAHA7 randomized clinical trial","volume":"14","author":"Attar","year":"2023","journal-title":"Stem Cell Res. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1161\/CIRCRESAHA.118.314653","article-title":"Potential Strategies for Clinical Translation of Repeated Cell Therapy","volume":"124","author":"Vrtovec","year":"2019","journal-title":"Circ. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.1093\/cvr\/cvae219","article-title":"Coming around again","volume":"120","author":"Savko","year":"2024","journal-title":"Cardiovasc. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2764","DOI":"10.1161\/CIRCULATIONAHA.113.002863","article-title":"Validation of contrast-enhanced magnetic resonance imaging to monitor regenerative efficacy after cell therapy in a porcine model of convalescent myocardial infarction","volume":"128","author":"Malliaras","year":"2013","journal-title":"Circulation"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1007\/s00395-024-01083-9","article-title":"The IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT): Multicenter pig study on the effect of ischemic preconditioning","volume":"119","author":"Kleinbongard","year":"2024","journal-title":"Basic Res. Cardiol."},{"key":"ref_21","first-page":"1074248420941672","article-title":"Intracoronary Administration of Allogeneic Cardiosphere-Derived Cells Immediately Prior to Reperfusion in Pigs with Acute Myocardial Infarction Reduces Infarct Size and Attenuates Adverse Cardiac Remodeling","volume":"26","author":"Sousonis","year":"2020","journal-title":"J. Cardiovasc. Pharmacol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Crisostomo, V., Baez-Diaz, C., Blanco-Blazquez, V., Alvarez, V., Lopez-Nieto, E., Maestre, J., Bayes-Genis, A., Galvez-Monton, C., Casado, J.G., and Sanchez-Margallo, F.M. (2021). The epicardial delivery of cardiosphere derived cells or their extracellular vesicles is safe but of limited value in experimental infarction. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-01728-y"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1186\/s13287-019-1237-6","article-title":"Dose-dependent improvement of cardiac function in a swine model of acute myocardial infarction after intracoronary administration of allogeneic heart-derived cells","volume":"10","author":"Crisostomo","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1093\/eurheartj\/ehp342","article-title":"Repeated implantation of skeletal myoblast in a swine model of chronic myocardial infarction","volume":"31","author":"Gavira","year":"2009","journal-title":"Eur. Heart J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/S0140-6736(00)03617-5","article-title":"Myoblast transplantation for heart failure","volume":"357","author":"Menasche","year":"2001","journal-title":"Lancet"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e003301","DOI":"10.1136\/openhrt-2025-003301","article-title":"Safety and efficacy of stem cell therapy in acute myocardial infarction: A systematic review and meta-analysis of adverse events, infarct size and LV ejection fraction assessed by CMRI","volume":"12","author":"Dede","year":"2025","journal-title":"Open Heart"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1161\/CIRCRESAHA.118.313795","article-title":"Perspectives on Directions and Priorities for Future Preclinical Studies in Regenerative Medicine","volume":"124","author":"Madonna","year":"2019","journal-title":"Circ. Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1161\/CIRCULATIONAHA.108.779900","article-title":"Stem Cell Therapy Is Proarrhythmic","volume":"119","author":"Macia","year":"2009","journal-title":"Circulation"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"B\u00e1ez-D\u00edaz, C., Torrescusa-Bermejo, A., S\u00e1nchez-Margallo, F.M., V\u00e1zquez-L\u00f3pez, F., Pulido, M., L\u00f3pez, E., Arenal, \u00c1., and Cris\u00f3stomo, V. (2025). Intracoronary-Cardiosphere-Derived Cell Secretome Therapy: Effects on Ventricular Tachycardia Inducibility and Cardiac Function in a Swine Model. Biomedicines, 13.","DOI":"10.3390\/biomedicines13051043"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1253\/circj.CJ-10-0898","article-title":"Repeated Intracoronary Infusion of Peripheral Blood Stem Cells With G-CSF in Patients with Refractory Ischemic Heart Failure; A Pilot Study","volume":"75","author":"Gu","year":"2011","journal-title":"Circ. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1093\/eurjhf\/hfp062","article-title":"Repeated autologous bone marrow mononuclear cell therapy in patients with large myocardial infarction","volume":"11","author":"Yao","year":"2009","journal-title":"Eur. J. Heart Fail."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.ejheart.2008.05.010","article-title":"Effect of repeated intracoronary injection of bone marrow cells in patients with ischaemic heart failure The Danish Stem Cell study\u2014Congestive Heart Failure trial (DanCell-CHF)","volume":"10","author":"Diederichsen","year":"2008","journal-title":"Eur. J. Heart Fail."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e002740","DOI":"10.1161\/CIRCINTERVENTIONS.115.002740","article-title":"Repeated Intramyocardial Bone Marrow Cell Injection in Previously Responding Patients with Refractory Angina Again Improves Myocardial Perfusion, Anginal Complaints, and Quality of Life","volume":"8","author":"Mann","year":"2015","journal-title":"Circ. Cardiovasc. Interv."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3738","DOI":"10.1161\/CIRCULATIONAHA.105.561423","article-title":"Influence of Ejection Fraction on Cardiovascular Outcomes in a Broad Spectrum of Heart Failure Patients","volume":"112","author":"Solomon","year":"2005","journal-title":"Circulation"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1161\/ATVBAHA.107.155317","article-title":"Cell-Based Therapy of Myocardial Infarction","volume":"28","author":"Dimmeler","year":"2008","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5937","DOI":"10.1111\/jcmm.15180","article-title":"Cardiac metabolism as a driver and therapeutic target of myocardial infarction","volume":"24","author":"Zuurbier","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"177","DOI":"10.4196\/kjpp.2023.27.2.177","article-title":"KLF9 deficiency protects the heart from inflammatory injury triggered by myocardial infarction","volume":"27","author":"Chang","year":"2023","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1865","DOI":"10.1016\/S0002-9440(10)65060-2","article-title":"Disruption of the Plasminogen Gene in Mice Abolishes Wound Healing after Myocardial Infarction","volume":"156","author":"Creemers","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1016\/j.mehy.2013.02.024","article-title":"Ephrin\u2013Eph signaling as a potential therapeutic target for the treatment of myocardial infarction","volume":"80","author":"Griffin","year":"2013","journal-title":"Med. Hypotheses"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"119595","DOI":"10.1016\/j.lfs.2021.119595","article-title":"EphA4 is highly expressed in the atria of heart and its deletion leads to atrial hypertrophy and electrocardiographic abnormalities in rats","volume":"278","author":"Li","year":"2021","journal-title":"Life Sci."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Zhang, F., Wang, L., Chen, Q., Zhang, F., Wang, X., and Yao, F. (2024). Podocan unraveled: Understanding its role in tumor proliferation and smooth muscle regulation. Biomed. Pharmacother., 179.","DOI":"10.1016\/j.biopha.2024.117416"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"RP89377","DOI":"10.7554\/eLife.89377.4","article-title":"Resident and recruited macrophages differentially contribute to cardiac healing after myocardial ischemia","volume":"12","author":"Weinberger","year":"2024","journal-title":"eLife"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Leinhos, L., Robinson, P., Poloni, G., Broadway-Stringer, S., Beglov, J., Lokman, A.B., Douglas, G., Nuthay, S., Fonseka, O., and Schmid, M. (2025). An ALPK3 truncation variant causing autosomal dominant hypertrophic cardiomyopathy is partially rescued by mavacamten. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-94371-w"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.1161\/CIRCULATIONAHA.122.059688","article-title":"Pathogenesis of Cardiomyopathy Caused by Variants in ALPK3, an Essential Pseudokinase in the Cardiomyocyte Nucleus and Sarcomere","volume":"146","author":"Agarwal","year":"2022","journal-title":"Circulation"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1161\/CIRCULATIONAHA.122.062885","article-title":"Restoration of Cardiac Myosin Light Chain Kinase Ameliorates Systolic Dysfunction by Reducing Superrelaxed Myosin","volume":"147","author":"Hitsumoto","year":"2023","journal-title":"Circulation"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"28723","DOI":"10.1074\/jbc.M110.147868","article-title":"Ankyrin-B Regulates Kir6.2 Membrane Expression and Function in Heart","volume":"285","author":"Li","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1016\/j.hrthm.2017.07.032","article-title":"The evolving role of ankyrin-B in cardiovascular disease","volume":"14","author":"Koenig","year":"2017","journal-title":"Heart Rhythm"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Pham, C., Mu\u00f1oz-Mart\u00edn, N., and Lodder, E.M. (2021). The Diverse Roles of TNNI3K in Cardiac Disease and Potential for Treatment. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22126422"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.1253\/circj.CJ-14-0543","article-title":"Troponin I-Interacting Protein Kinase\u2013 A Novel Cardiac-Specific Kinase, Emerging as a Molecular Target for the Treatment of Cardiac Disease","volume":"78","author":"Lal","year":"2014","journal-title":"Circ. J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"H708","DOI":"10.1152\/ajpheart.00252.2008","article-title":"Overexpression of TNNI3K, a cardiac-specific MAP kinase, promotes P19CL6-derived cardiac myogenesis and prevents myocardial infarction-induced injury","volume":"295","author":"Lai","year":"2008","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5456","DOI":"10.1002\/ehf2.13640","article-title":"Prognostic impact of follow-up serum albumin after acute myocardial infarction","volume":"8","author":"Yoshioka","year":"2021","journal-title":"ESC Heart Fail."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1159\/000430174","article-title":"TRAP1 Provides Protection Against Myocardial Ischemia-Reperfusion Injury by Ameliorating Mitochondrial Dysfunction","volume":"36","author":"Zhang","year":"2015","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.jjcc.2016.05.020","article-title":"Phosphorylated eEF2 is SUMOylated and induces cardiomyocyte apoptosis during myocardial ischemia reperfusion","volume":"69","author":"Zhang","year":"2017","journal-title":"J. Cardiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"C1079","DOI":"10.1152\/ajpcell.00285.2019","article-title":"Cell type- and tissue-specific functions of ecto-5\u2032-nucleotidase (CD73)","volume":"317","author":"Minor","year":"2019","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Rajlic, S., Surmann, L., Zimmermann, P., Weisheit, C.K., Bindila, L., Treede, H., Velten, M., Daiber, A., and Duerr, G.D. (2022). Fatty Acid Amide Hydrolase Deficiency Is Associated with Deleterious Cardiac Effects after Myocardial Ischemia and Reperfusion in Mice. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232012690"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1007\/s00432-025-06285-9","article-title":"Research and development prospects of TRIM65","volume":"151","author":"Deng","year":"2025","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"\u00c1lvarez, V., Casado, J.G., Bl\u00e1zquez, R., Marinaro, F., de Pedro, M.d.l.\u00c1., Pulido, M., and Nieto, E.L. (2022). Isolation, culture and, characterization of Cardiosphere-Derived Cells (CDCs). Protoc. Exch.","DOI":"10.21203\/rs.3.pex-1455\/v1"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jcyt.2015.11.008","article-title":"International Society for Cellular Therapy perspective on immune functional assays for mesenchymal stromal cells as potency release criterion for advanced phase clinical trials","volume":"18","author":"Galipeau","year":"2016","journal-title":"Cytotherapy"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Binek, A., Castans, C., Jorge, I., Bagwan, N., Rodr\u00edguez, J.M., Fern\u00e1ndez-Jim\u00e9nez, R., Gal\u00e1n-Arriola, C., Oliver, E., G\u00f3mez, M., and Clemente-Morag\u00f3n, A. (2024). Oxidative Post-translational Protein Modifications upon Ischemia\/Reperfusion Injury. Antioxidants, 13.","DOI":"10.3390\/antiox13010106"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"103624","DOI":"10.1016\/j.jprot.2019.103624","article-title":"Improved integrative analysis of the thiol redox proteome using filter-aided sample preparation","volume":"214","author":"Camafeita","year":"2020","journal-title":"J. Proteom."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Orsburn, B.C. (2021). Proteome Discoverer\u2014A Community Enhanced Data Processing Suite for Protein Informatics. Proteomes, 9.","DOI":"10.3390\/proteomes9010015"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"D523","DOI":"10.1093\/nar\/gkac1052","article-title":"UniProt: The Universal Protein Knowledgebase in 2023","volume":"51","author":"Consortium","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"176","DOI":"10.4172\/jpb.1000404","article-title":"DecoyPyrat: Fast Non-redundant Hybrid Decoy Sequence Generation for Large Scale Proteomics","volume":"9","author":"Wright","year":"2016","journal-title":"J. Proteom. Bioinform."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5383","DOI":"10.1021\/ac025747h","article-title":"Empirical Statistical Model to Estimate the Accuracy of Peptide Identifications Made by MS\/MS and Database Search","volume":"74","author":"Keller","year":"2002","journal-title":"Anal. Chem."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1021\/acs.jproteome.9b00819","article-title":"Protein Probability Model for High-Throughput Protein Identification by Mass Spectrometry-Based Proteomics","volume":"19","author":"Prieto","year":"2020","journal-title":"J. Proteome Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1021\/pr5007284","article-title":"Revisiting Peptide Identification by High-Accuracy Mass Spectrometry: Problems Associated with the Use of Narrow Mass Precursor Windows","volume":"14","year":"2015","journal-title":"J. Proteome Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1021\/pr4006958","article-title":"General Statistical Framework for Quantitative Proteomics by Stable Isotope Labeling","volume":"13","author":"Navarro","year":"2014","journal-title":"J. Proteome Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1074\/mcp.M115.055905","article-title":"A Novel Systems-Biology Algorithm for the Analysis of Coordinated Protein Responses Using Quantitative Proteomics","volume":"15","author":"Camafeita","year":"2016","journal-title":"Mol. Cell. Proteom."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1016\/j.csbj.2023.12.034","article-title":"iSanXoT: A standalone application for the integrative analysis of mass spectrometry-based quantitative proteomics data","volume":"23","author":"Jorge","year":"2024","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_70","doi-asserted-by":"crossref","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":"ref_71","doi-asserted-by":"crossref","first-page":"W216","DOI":"10.1093\/nar\/gkac194","article-title":"DAVID: A web server for functional enrichment analysis and functional annotation of gene lists (2021 update)","volume":"50","author":"Sherman","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/nprot.2008.211","article-title":"Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources","volume":"4","author":"Huang","year":"2009","journal-title":"Nat. Protoc."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Chin, C.-H., Chen, S.-H., Wu, H.-H., Ho, C.-W., Ko, M.-T., and Lin, C.-Y. (2014). cytoHubba: Identifying hub objects and sub-networks from complex interactome. BMC Syst. Biol., 8.","DOI":"10.1186\/1752-0509-8-S4-S11"},{"key":"ref_74","first-page":"D543","article-title":"The PRIDE database resources in 2022: A hub for mass spectrometry-based proteomics evidences","volume":"50","author":"Bai","year":"2021","journal-title":"Nucleic Acids Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11294\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T05:19:15Z","timestamp":1764047955000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/23\/11294"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,22]]},"references-count":74,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262311294"],"URL":"https:\/\/doi.org\/10.3390\/ijms262311294","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,11,22]]}}}