{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T10:10:45Z","timestamp":1769076645484,"version":"3.49.0"},"reference-count":59,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T00:00:00Z","timestamp":1635724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI20\/01469, PI20\/00071, CP18\/00145"],"award-info":[{"award-number":["PI20\/01469, PI20\/00071, CP18\/00145"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centro de Investigaci\u00f3n en Red en Enfermedades Cardiovasculares","award":["CB16\/11\/00261"],"award-info":[{"award-number":["CB16\/11\/00261"]}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["ERDF, \"A way to make Europe\""],"award-info":[{"award-number":["ERDF, \"A way to make Europe\""]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Although the roles of telomeres and oxidative stress in ischaemic cardiomyopathy (ICM) are known, mechanisms of telomere homeostasis and their relationship with oxidative stress are incompletely understood. We performed two RNA-seq analyses (mRNA n = 23; ncRNA n = 30) and protein validation on left ventricles of explanted hearts from ICM and control subjects. We observed dysregulation of the shelterin and cohesin complexes, which was related to an increase in the response to cellular oxidative stress. Moreover, we found alterations at mRNA level in the mechanisms of telomeric DNA repair. Specifically, increased RAD51D mRNA levels were correlated with left ventricular diameters. RAD51D protein levels were unaltered, however, and were inversely corelated with the miR-103a-3p upregulation. We also observed the overexpression of lncRNAs (TERRA and GUARDIN) involved in telomere protection in response to stress and alterations in their regulatory molecules. Expression of the TERRA transcription factor ATF7 was correlated with superoxide dismutase 1 expression and left ventricular diameters. The levels of GUARDIN and its transcription factor FOSL2 were correlated with those of catalase. Therefore, we showed specific alterations in the mechanisms of telomeric DNA repair and protection, and these alterations are related to an increase in the response mechanisms to oxidative stress and cardiac dysfunction in ICM.<\/jats:p>","DOI":"10.3390\/antiox10111750","type":"journal-article","created":{"date-parts":[[2021,11,1]],"date-time":"2021-11-01T11:47:38Z","timestamp":1635767258000},"page":"1750","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Relationships of Telomere Homeostasis with Oxidative Stress and Cardiac Dysfunction in Human Ischaemic Hearts"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3466-2558","authenticated-orcid":false,"given":"Estefan\u00eda","family":"Taraz\u00f3n","sequence":"first","affiliation":[{"name":"Myocardial Dysfunction and Cardiac Transplantation Unit, Health Research Institute Hospital La Fe (IIS La Fe), 46026 Valencia, Spain"},{"name":"CIBERCV, Institute of Health Carlos III, C\/Monforte de Lemos 3\u20135, Pabell\u00f3n 11, Planta 0, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorena","family":"P\u00e9rez-Carrillo","sequence":"additional","affiliation":[{"name":"Myocardial Dysfunction and Cardiac Transplantation Unit, Health Research Institute Hospital La Fe (IIS La Fe), 46026 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isaac","family":"Gim\u00e9nez-Escamilla","sequence":"additional","affiliation":[{"name":"Myocardial Dysfunction and Cardiac Transplantation Unit, Health Research Institute Hospital La Fe (IIS La Fe), 46026 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pablo","family":"Ramos-Castellanos","sequence":"additional","affiliation":[{"name":"Myocardial Dysfunction and Cardiac Transplantation Unit, Health Research Institute Hospital La Fe (IIS La Fe), 46026 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Mart\u00ednez-Dolz","sequence":"additional","affiliation":[{"name":"Myocardial Dysfunction and Cardiac Transplantation Unit, Health Research Institute Hospital La Fe (IIS La Fe), 46026 Valencia, Spain"},{"name":"CIBERCV, Institute of Health Carlos III, C\/Monforte de Lemos 3\u20135, Pabell\u00f3n 11, Planta 0, 28029 Madrid, Spain"},{"name":"Heart Failure and Transplantation Unit, Cardiology Department, University and Polytechnic La Fe Hospital, 46026 Valencia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4415-7160","authenticated-orcid":false,"given":"Manuel","family":"Portol\u00e9s","sequence":"additional","affiliation":[{"name":"Myocardial Dysfunction and Cardiac Transplantation Unit, Health Research Institute Hospital La Fe (IIS La Fe), 46026 Valencia, Spain"},{"name":"CIBERCV, Institute of Health Carlos III, C\/Monforte de Lemos 3\u20135, Pabell\u00f3n 11, Planta 0, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Esther","family":"Rosell\u00f3-Llet\u00ed","sequence":"additional","affiliation":[{"name":"Myocardial Dysfunction and Cardiac Transplantation Unit, Health Research Institute Hospital La Fe (IIS La Fe), 46026 Valencia, Spain"},{"name":"CIBERCV, Institute of Health Carlos III, C\/Monforte de Lemos 3\u20135, Pabell\u00f3n 11, Planta 0, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1093\/eurheartj\/ehw128","article-title":"2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC)Developed with the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"37","author":"Ponikowski","year":"2016","journal-title":"Eur. 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