Apolipoprotein E4 Is Associated with Right Ventricular Dysfunction in Dilated Cardiomyopathy—An Animal and In-Human Comparative Study
International Journal of Molecular Sciences, vol. 22, pp. 9688
Abstract
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−/− rats, mostly after a high-fat diet. Interestingly, the right ventricle of apoE−/− 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 (χ2 = 10.244; p = 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, p < 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, p = 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.
Authors 15
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University of Medicine and Pharmacy of Craiova
Affiliation as printed
Department of Cardiology, University of Medicine and Pharmacy, 200349 Craiova, Romania
Human Genetic Laboratory, Faculty of Medicine, University of Medicine and Pharmacy, 200349 Craiova, Romania
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Affiliation as printed
Department of Cardiology, Angiology and Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany
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Cairo University · RWTH Aachen University
Affiliation as printed
Department of Cardiology, Angiology and Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany
Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt
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Affiliation as printed
Medical Faculty, Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany
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Affiliation as printed
Department of Cardiology, Angiology and Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany
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Roberta Andreea Florescu Aachen Department of Cardiology, Angiology and Intensive Care Medical Faculty
Affiliation as printed
Department of Cardiology, Angiology and Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany
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Düsseldorf University Hospital
Affiliation as printed
Department for Pharmacology and Clinical Pharmacology, Medical Faculty, University Hospital Düsseldorf, 40225 Düsseldorf, Germany
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Affiliation as printed
Department of Cardiology, Angiology and Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany
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David Schumacher Aachen Department of Anesthesiology, Medical Faculty Medical Faculty Institute of Experimental Medicine and Systems Biology
Affiliation as printed
Department of Anesthesiology, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany
Medical Faculty, Institute of Experimental Medicine and Systems Biology, RWTH Aachen University, 52074 Aachen, Germany
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University of Medicine and Pharmacy of Craiova
Affiliation as printed
Human Genetic Laboratory, Faculty of Medicine, University of Medicine and Pharmacy, 200349 Craiova, Romania
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University of Medicine and Pharmacy of Craiova
Affiliation as printed
Human Genetic Laboratory, Faculty of Medicine, University of Medicine and Pharmacy, 200349 Craiova, Romania
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University of Medicine and Pharmacy of Craiova
Affiliation as printed
Department of Cardiology, University of Medicine and Pharmacy, 200349 Craiova, Romania
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University of Medicine and Pharmacy of Craiova
Affiliation as printed
Department of Cardiology, University of Medicine and Pharmacy, 200349 Craiova, Romania
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Affiliation as printed
Department of Cardiology, Angiology and Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany
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Elisa Anamaria Liehn corresponding Aachen Department of Cardiology, Angiology and Intensive Care Medical Faculty Institute for Molecular Cardiovascular Research (IMCAR)
University of Medicine and Pharmacy of Craiova · Institutul National Victor Babes · RWTH Aachen University
Affiliation as printed
Department of Cardiology, Angiology and Intensive Care, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany
Human Genetic Laboratory, Faculty of Medicine, University of Medicine and Pharmacy, 200349 Craiova, Romania
Institute for Pathology “Victor Babes”, 050096 Bucharest, Romania
Medical Faculty, Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen University, 52074 Aachen, Germany
Institute for Pathology "Victor Babes", 050096 Bucharest, Romania
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