{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T02:33:58Z","timestamp":1786242838756,"version":"build-2736575974"},"reference-count":37,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hospital Universitari de Bellvitge and Bellvitge Biomedical Research Institute","award":["PR066\/17"],"award-info":[{"award-number":["PR066\/17"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Primary graft dysfunction (PGD) remains a major cause of early morbidity and mortality after a heart transplant (HTx). Understanding the donor-related mechanisms involved may help improve organ selection and post-HTx outcomes. This study aimed to explore the association between the donor serum biomarkers of cell death and inflammation and the incidence of PGD and rejection in HTx recipients. We conducted a retrospective, multicenter observational study of brain-dead (DBD) heart donors and corresponding recipients between 2013 and 2019. Donor blood samples were analyzed for inflammatory cytokines, cell death-related proteins, and mitochondrial (mtDNA) and genomic DNA (gDNA). A total of 39 donor\u2013recipient pairs were included. Sixteen recipients developed severe PGD, and five experienced \u22652R cellular rejection. Donors whose recipients developed PGD had significantly lower serum Caspase-3 levels compared to those without PGD (391.6 [101.8\u20131003.3] vs. 65.3 [40.2\u2013163.3] pg\/mL; p = 0.04). A trend toward lower mtDNA\/gDNA ratio was also observed in the same group (10.5 [5.4\u201324.6] vs. 6.5 [3.3\u201310.7]; p = 0.067). Lower Caspase-3 levels in donor serum were significantly associated with the development of severe PGD in recipients. This may suggest that the sublethal activation of apoptotic pathways in the donor could play a protective role, potentially conditioning the graft to tolerate ischemic injury.<\/jats:p>","DOI":"10.3390\/ijms26199434","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T13:30:03Z","timestamp":1758893403000},"page":"9434","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Caspase-3 in Brain Death Donors Is Associated with Reduced Primary Graft Dysfunction After Heart Transplantation"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3196-4975","authenticated-orcid":false,"given":"Lorena","family":"Herrador","sequence":"first","affiliation":[{"name":"Heart Failure and Heart Transplant Unit, Cardiology Department, Bio-Heart Cardiovascular Diseases Research Group, Hospital Universitari de Bellvitge, Universitat de Barcelona, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08908 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Gonz\u00e1lez-Costello","sequence":"additional","affiliation":[{"name":"Heart Failure and Heart Transplant Unit, Cardiology Department, Bio-Heart Cardiovascular Diseases Research Group, Hospital Universitari de Bellvitge, Universitat de Barcelona, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"},{"name":"Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08908 Barcelona, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Niubo-Bosch","sequence":"additional","affiliation":[{"name":"Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08908 Barcelona, Spain"},{"name":"Microbiology Department, Hospital Universitari de Bellvitge, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Calatayud-Samper","sequence":"additional","affiliation":[{"name":"Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08908 Barcelona, Spain"},{"name":"Microbiology Department, Hospital Universitari de Bellvitge, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"Maestro-Benedicto","sequence":"additional","affiliation":[{"name":"Heart Failure and Heart Transplant Unit, Cardiology Department, Hospital de la Santa Creu i Sant Pau, 08025 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Farrero-Torres","sequence":"additional","affiliation":[{"name":"Heart Failure and Heart Transplant Unit, Cardiology Department, Hospital Cl\u00ednic Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2047-281X","authenticated-orcid":false,"given":"Teresa","family":"Blasco-Peiro","sequence":"additional","affiliation":[{"name":"Heart Failure and Heart Transplant Unit, Cardiology Department, Hospital Universitario Miguel Servet, 50009 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Almenar-Bonet","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"},{"name":"Heart Failure and Heart Transplant Unit, Cardiology Department, Hospital Universitario y Polit\u00e9cnico La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zorba","family":"Bl\u00e1zquez-Bermejo","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"},{"name":"Heart Failure and Heart Transplantation Unit, Cardiology Department, Hospital General Universitario Gregorio Mara\u00f1\u00f3n, 28007 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Garrido-Bravo","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain"},{"name":"Heart Failure and Heart Transplantation Unit, Cardiology Department, Hospital Universitario Virgen de la Arrixaca, 30120 Murcia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9076-241X","authenticated-orcid":false,"given":"Ferran","family":"Gran-Ipi\u00f1a","sequence":"additional","affiliation":[{"name":"Pediatric Heart Transplant Unit, Pediatric Cardiology and Pediatric Cardiac Surgery Department, Hospital Vall Hebron, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9398-5229","authenticated-orcid":false,"given":"Antonio","family":"Grande-Trillo","sequence":"additional","affiliation":[{"name":"Heart Failure and Heart Transplantation Unit, Cardiology Department, Hospital Universitario Virgen del Roc\u00edo, 41013 Sevilla, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Manito","sequence":"additional","affiliation":[{"name":"Heart Failure and Heart Transplant Unit, Cardiology Department, Bio-Heart Cardiovascular Diseases Research Group, Hospital Universitari de Bellvitge, Universitat de Barcelona, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3281-1126","authenticated-orcid":false,"given":"Gabriel","family":"Moreno-Gonzalez","sequence":"additional","affiliation":[{"name":"Bellvitge Biomedical Research Institute (IDIBELL), L\u2019Hospitalet de Llobregat, 08908 Barcelona, Spain"},{"name":"Intensive Care Unit, Hospital Universitari de Bellvitge, L\u2019Hospitalet de Llobregat, 08907 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"key":"ref_1","first-page":"923","article-title":"Spanish heart transplant registry. 33rd official report of the Heart failure Association of the Spanish Society of Cardiology","volume":"75","year":"2022","journal-title":"Rev. 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