{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T19:02:31Z","timestamp":1789758151839,"version":"4.0.1"},"reference-count":40,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T00:00:00Z","timestamp":1630972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Project-IDs 322900939, 454024652, 432698239 and 432698239"],"award-info":[{"award-number":["Project-IDs 322900939, 454024652, 432698239 and 432698239"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["Project-IDs GZ VO 1624\/5-1"],"award-info":[{"award-number":["Project-IDs GZ VO 1624\/5-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009398","name":"Medizinische Fakult\u00e4t, RWTH Aachen University","doi-asserted-by":"publisher","award":["Clinician Scientist Program"],"award-info":[{"award-number":["Clinician Scientist Program"]}],"id":[{"id":"10.13039\/501100009398","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009398","name":"Medizinische Fakult\u00e4t, RWTH Aachen University","doi-asserted-by":"publisher","award":["Interdiciplinary Center for Clinical Research IZKF Aachen (junior research group E.A.L.)"],"award-info":[{"award-number":["Interdiciplinary Center for Clinical Research IZKF Aachen (junior research group E.A.L.)"]}],"id":[{"id":"10.13039\/501100009398","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>ApoE abnormality represents a well-known risk factor for cardiovascular diseases. Beyond its role in lipid metabolism, novel studies demonstrate a complex involvement of apoE in membrane homeostasis and signaling as well as in nuclear transcription. Due to the large spread of apoE isoforms in the human population, there is a need to understand the apoE\u2019s role in pathological processes. Our study aims to dissect the involvement of apoE in heart failure. We showed that apoE-deficient rats present multiple organ damages (kidney, liver, lung and spleen) besides the known predisposition for obesity and affected lipid metabolism (two-fold increase in tissular damages in liver and one-fold increase in kidney, lung and spleen). Heart tissue also showed significant morphological changes in apoE\u2212\/\u2212 rats, mostly after a high-fat diet. Interestingly, the right ventricle of apoE\u2212\/\u2212 rats fed a high-fat diet showed more damage and affected collagen content (~60% less total collagen content and double increase in collagen1\/collagen3 ratio) compared with the left ventricle (no significant differences in total collagen content or collagen1\/collagen3 ratio). In patients, we were able to find a correlation between the presence of \u03b54 allele and cardiomyopathy (\u03c72 = 10.244; p = 0.001), but also with right ventricle dysfunction with decreased TAPSE (15.3 \u00b1 2.63 mm in \u03b54-allele-presenting patients vs. 19.8 \u00b1 3.58 mm if the \u03b54 allele is absent, p &lt; 0.0001*) and increased in systolic pulmonary artery pressure (50.44 \u00b1 16.47 mmHg in \u03b54-allele-presenting patients vs. 40.68 \u00b1 15.94 mmHg if the \u03b54 allele is absent, p = 0.0019). Our results confirm that the presence of the \u03b54 allele is a lipid-metabolism-independent risk factor for heart failure. Moreover, we show for the first time that the presence of the \u03b54 allele is associated with right ventricle dysfunction, implying different regulatory mechanisms of fibroblasts and the extracellular matrix in both ventricles. This is essential to be considered and thoroughly investigated before the design of therapeutical strategies for patients with heart failure.<\/jats:p>","DOI":"10.3390\/ijms22189688","type":"journal-article","created":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T10:24:25Z","timestamp":1631010265000},"page":"9688","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Apolipoprotein E4 Is Associated with Right Ventricular Dysfunction in Dilated Cardiomyopathy\u2014An Animal and In-Human Comparative Study"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6936-6279","authenticated-orcid":false,"given":"Rodica","family":"Diaconu","sequence":"first","affiliation":[{"name":"Human Genetic Laboratory, Faculty of Medicine, University of Medicine and Pharmacy, 200349 Craiova, Romania"},{"name":"Department of Cardiology, University of Medicine and Pharmacy, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Schaaps","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamdouh","family":"Afify","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"},{"name":"Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9921-4284","authenticated-orcid":false,"given":"Peter","family":"Boor","sequence":"additional","affiliation":[{"name":"Medical Faculty, Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Cornelissen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta A.","family":"Florescu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakine","family":"Simsekyilmaz","sequence":"additional","affiliation":[{"name":"Department for Pharmacology and Clinical Pharmacology, Medical Faculty, University Hospital D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teddy","family":"El-Khoury","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2308-6543","authenticated-orcid":false,"given":"David","family":"Schumacher","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"},{"name":"Medical Faculty, Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai","family":"Ioana","sequence":"additional","affiliation":[{"name":"Human Genetic Laboratory, Faculty of Medicine, University of Medicine and Pharmacy, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana","family":"Streata","sequence":"additional","affiliation":[{"name":"Human Genetic Laboratory, Faculty of Medicine, University of Medicine and Pharmacy, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantin","family":"Militaru","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Medicine and Pharmacy, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6338-2657","authenticated-orcid":false,"given":"Ionut","family":"Donoiu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University of Medicine and Pharmacy, 200349 Craiova, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Vogt","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Angiology and Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1253-3272","authenticated-orcid":false,"given":"Elisa A.","family":"Liehn","sequence":"additional","affiliation":[{"name":"Human Genetic Laboratory, Faculty of Medicine, University of Medicine and Pharmacy, 200349 Craiova, Romania"},{"name":"Department of Cardiology, Angiology and Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany"},{"name":"Medical Faculty, Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany"},{"name":"Institute for Pathology \u201cVictor Babes\u201d, 050096 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1097\/01.ASN.0000045048.71975.FC","article-title":"The apolipoprotein e knockout mouse: A model documenting accelerated atherogenesis in uremia","volume":"14","author":"Buzello","year":"2003","journal-title":"J. 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