Apolipoprotein E4 Is Associated with Right Ventricular Dysfunction in Dilated Cardiomyopathy—An Animal and In-Human Comparative Study
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 hu...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/18/9688 |
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| author | Rodica Diaconu Nicole Schaaps Mamdouh Afify Peter Boor Anne Cornelissen Roberta A. Florescu Sakine Simsekyilmaz Teddy El-Khoury David Schumacher Mihai Ioana Ioana Streata Constantin Militaru Ionut Donoiu Felix Vogt Elisa A. Liehn |
| author_facet | Rodica Diaconu Nicole Schaaps Mamdouh Afify Peter Boor Anne Cornelissen Roberta A. Florescu Sakine Simsekyilmaz Teddy El-Khoury David Schumacher Mihai Ioana Ioana Streata Constantin Militaru Ionut Donoiu Felix Vogt Elisa A. Liehn |
| author_sort | Rodica Diaconu |
| collection | DOAJ |
| description | 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’s 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<sup>−/−</sup> rats, mostly after a high-fat diet. Interestingly, the right ventricle of apoE<sup>−/−</sup> 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 ε4 allele and cardiomyopathy (χ<sup>2</sup> = 10.244; <i>p</i> = 0.001), but also with right ventricle dysfunction with decreased TAPSE (15.3 ± 2.63 mm in ε4-allele-presenting patients vs. 19.8 ± 3.58 mm if the ε4 allele is absent, <i>p</i> < 0.0001*) and increased in systolic pulmonary artery pressure (50.44 ± 16.47 mmHg in ε4-allele-presenting patients vs. 40.68 ± 15.94 mmHg if the ε4 allele is absent, <i>p</i> = 0.0019). Our results confirm that the presence of the ε4 allele is a lipid-metabolism-independent risk factor for heart failure. Moreover, we show for the first time that the presence of the ε4 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. |
| first_indexed | 2024-03-10T07:36:59Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T07:36:59Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a864240947514f728b7a5ddfc16774522023-11-22T13:25:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-012218968810.3390/ijms22189688Apolipoprotein E4 Is Associated with Right Ventricular Dysfunction in Dilated Cardiomyopathy—An Animal and In-Human Comparative StudyRodica Diaconu0Nicole Schaaps1Mamdouh Afify2Peter Boor3Anne Cornelissen4Roberta A. Florescu5Sakine Simsekyilmaz6Teddy El-Khoury7David Schumacher8Mihai Ioana9Ioana Streata10Constantin Militaru11Ionut Donoiu12Felix Vogt13Elisa A. Liehn14Human Genetic Laboratory, Faculty of Medicine, University of Medicine and Pharmacy, 200349 Craiova, RomaniaDepartment of Cardiology, Angiology and Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, GermanyDepartment of Cardiology, Angiology and Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, GermanyMedical Faculty, Institute of Pathology, RWTH Aachen University, 52074 Aachen, GermanyDepartment of Cardiology, Angiology and Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, GermanyDepartment of Cardiology, Angiology and Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, GermanyDepartment for Pharmacology and Clinical Pharmacology, Medical Faculty, University Hospital Düsseldorf, 40225 Düsseldorf, GermanyDepartment of Cardiology, Angiology and Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, GermanyDepartment of Anesthesiology, Medical Faculty, RWTH Aachen University, 52074 Aachen, GermanyHuman Genetic Laboratory, Faculty of Medicine, University of Medicine and Pharmacy, 200349 Craiova, RomaniaHuman Genetic Laboratory, Faculty of Medicine, University of Medicine and Pharmacy, 200349 Craiova, RomaniaDepartment of Cardiology, University of Medicine and Pharmacy, 200349 Craiova, RomaniaDepartment of Cardiology, University of Medicine and Pharmacy, 200349 Craiova, RomaniaDepartment of Cardiology, Angiology and Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, GermanyHuman Genetic Laboratory, Faculty of Medicine, University of Medicine and Pharmacy, 200349 Craiova, RomaniaApoE 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’s 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<sup>−/−</sup> rats, mostly after a high-fat diet. Interestingly, the right ventricle of apoE<sup>−/−</sup> 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 ε4 allele and cardiomyopathy (χ<sup>2</sup> = 10.244; <i>p</i> = 0.001), but also with right ventricle dysfunction with decreased TAPSE (15.3 ± 2.63 mm in ε4-allele-presenting patients vs. 19.8 ± 3.58 mm if the ε4 allele is absent, <i>p</i> < 0.0001*) and increased in systolic pulmonary artery pressure (50.44 ± 16.47 mmHg in ε4-allele-presenting patients vs. 40.68 ± 15.94 mmHg if the ε4 allele is absent, <i>p</i> = 0.0019). Our results confirm that the presence of the ε4 allele is a lipid-metabolism-independent risk factor for heart failure. Moreover, we show for the first time that the presence of the ε4 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.https://www.mdpi.com/1422-0067/22/18/9688apoEcardiovascular modelsdilated cardiomyopathyright ventricular systolic dysfunctionε4 allele |
| spellingShingle | Rodica Diaconu Nicole Schaaps Mamdouh Afify Peter Boor Anne Cornelissen Roberta A. Florescu Sakine Simsekyilmaz Teddy El-Khoury David Schumacher Mihai Ioana Ioana Streata Constantin Militaru Ionut Donoiu Felix Vogt Elisa A. Liehn Apolipoprotein E4 Is Associated with Right Ventricular Dysfunction in Dilated Cardiomyopathy—An Animal and In-Human Comparative Study International Journal of Molecular Sciences apoE cardiovascular models dilated cardiomyopathy right ventricular systolic dysfunction ε4 allele |
| title | Apolipoprotein E4 Is Associated with Right Ventricular Dysfunction in Dilated Cardiomyopathy—An Animal and In-Human Comparative Study |
| title_full | Apolipoprotein E4 Is Associated with Right Ventricular Dysfunction in Dilated Cardiomyopathy—An Animal and In-Human Comparative Study |
| title_fullStr | Apolipoprotein E4 Is Associated with Right Ventricular Dysfunction in Dilated Cardiomyopathy—An Animal and In-Human Comparative Study |
| title_full_unstemmed | Apolipoprotein E4 Is Associated with Right Ventricular Dysfunction in Dilated Cardiomyopathy—An Animal and In-Human Comparative Study |
| title_short | Apolipoprotein E4 Is Associated with Right Ventricular Dysfunction in Dilated Cardiomyopathy—An Animal and In-Human Comparative Study |
| title_sort | apolipoprotein e4 is associated with right ventricular dysfunction in dilated cardiomyopathy an animal and in human comparative study |
| topic | apoE cardiovascular models dilated cardiomyopathy right ventricular systolic dysfunction ε4 allele |
| url | https://www.mdpi.com/1422-0067/22/18/9688 |
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