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Role of DNA methyltransferase 3a (Dnmt3a) in the adaptation of atherogenesis key players to proatherogenic environment.

Abstract : DNA methyltransferase 3a (DNMT3A) links environment to phenotypes via catalysis of CpG dinucleotides, notably found in genes promoter regions, methylation and whose hypomethylation is associated with gene transcriptional activation thus enabling the control of gene expression in physiologic and pathologic states. Most of our knowledge about its’ role in disease occurrence are based on articles demonstrating its’ implication in human cancers. Limited data from mouse studies illustrates its’ contribution to certain pathologies. Atherosclerosis constitutes the single most important contributor to the growing burden of cardiovascular disease. Risk factors contribute to disease occurrence, where most are related to environmental influences, notably Dyslipidaemia, a key initiator of atherosclerosis. Abundant data link hypercholesterolemia to atherogenesis, on the other hand, contribution of inflammatory mechanisms that couple dyslipidaemia to atheroma formation has been also appreciated. So far, a growing number of data suggests a role of Dnmt3a in atherosclerosis but to date, its role in cholesterol regulation and early plaque formation has not been clearly elucidated. Our results suggested that deletion of Dnmt3a in monocyte/macrophages does not affect the formation of early atherosclerostic plaque nor does it impact the polarization of macrophages in vitro. In parallel, we have also demonstrated that the deletion of Dnmt3a in hepatocytes leads to significant elevation in TC levels. We were not able to relate this elevation to dysregulation of major genes involved in Cholesterol regulation. On the other hand, we noticed activation of hepatic inflammatory responses.
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Maisa Nabulsi. Role of DNA methyltransferase 3a (Dnmt3a) in the adaptation of atherogenesis key players to proatherogenic environment.. Tissues and Organs [q-bio.TO]. Université Pierre et Marie Curie - Paris VI, 2016. English. ⟨NNT : 2016PA066739⟩. ⟨tel-01690462⟩

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