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Hypertrophie myocardique, risque vasculaire et métabolisme des monocarbones. Conséquences métaboliques et moléculaires dans un modèle de raton carencé en donneurs de méthyles, et chez le sujet âgé

Abstract : The deficiency in methyl donors is prevalent in the perinatal period of life and in aging. Dietary methyl donors, folate and vitamin B12, influence the cellular content in Sadenosylmethionine and S-adenosylhomocysteine and increases homocysteine. The link between methyl donors and energy metabolism is not known, despite their role in pathways related to epigenetics and synthesis of methylated molecules. We evaluated the consequences of a diet lacking methyl donors, in myocardium of weaning rats from dams subjected to deficiency during gestation and lactation. The deficient diet increased plasma homocysteine and myocardium Sadenosylhomocysteine. The results evidenced a hypertrophic cardiomyopathy with a global deficit in fatty acid oxidation with increased plasma acylcarnitines. The links between one-carbone metabolism, mitochondrial fatty acid oxidation and cardiomyopathy were ascertained by correlations between hyperhomocysteinemia, short-, medium- and long-chain acylcarnitines, and type-B natriuretic peptide. Methyl donor deficiency may be an aggravating condition of cardiomyopathy by impairing fatty acid oxidation through altered expression of PPAR[alpha] and ERR[alpha] and imbalanced acetylation/methylation of PGC1[alpha]. Finally, in a clinical study we sshowed that the Hcy and Apo A-I were two metabolic factors that influence the « anckle brachial index » in an ambulatory aged Sicilian population. The influence of homocysteine on Apo A-I and HDL metabolism provides new insights on its role on vascular diseases, at a cross-point between atherosclerosis and atherothrombosis
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https://hal.univ-lorraine.fr/tel-01746390
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Maira Alejandra Cardenas. Hypertrophie myocardique, risque vasculaire et métabolisme des monocarbones. Conséquences métaboliques et moléculaires dans un modèle de raton carencé en donneurs de méthyles, et chez le sujet âgé. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2011. Français. ⟨NNT : 2011NAN10004⟩. ⟨tel-01746390⟩

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