Perinatal Hypercholesterolemia Exacerbates Atherosclerosis Lesions in Offspring by Altering Metabolism of Trimethylamine-N-Oxide and Bile Acids

Trenteseaux, Charlotte; Gaston, Anh-Thu; Aguesse, Audrey; Poupeau, Guillaume; Coppet, Pierre de; Andriantsitohaina, Ramaroson; Khallou-Laschet, Jamila; Amarger, Valérie; Krempf, Michel; Nobécourt-Dupuy, Estelle; Ouguerram, Khadija

doi:10.1161/atvbaha.117.309923

Cited by 38 publications

(27 citation statements)

References 48 publications

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“…Consistent with this possibility, a recent study showed that female Apoe −/− mice with hypercholesterolemic mothers develop larger aortic root lesions compared with mice with normocholesterolemic mothers—an effect that was associated with TMAO levels in the offspring. 40 …”

Section: Discussionmentioning

confidence: 99%

Impact of Gut Microbiota and Diet on the Development of Atherosclerosis in Apoe ^−/− Mice

Jönsson

Caesar

Akrami

et al. 2018

ATVB

129

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Section: Discussionmentioning

confidence: 99%

Impact of Gut Microbiota and Diet on the Development of Atherosclerosis in Apoe ^−/− Mice

Jönsson

Caesar

Akrami

et al. 2018

ATVB

129

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“…For example, ApoE deficiency and postnatal exposure to hypercholesterolemic environment causes altered histone methylation patterns in the vasculature (Alkemade, et al, 2010). Recently, Trenteseaux et al (Trenteseaux, et al, 2017)evaluated the effect of perinatal hypercholesterolemia on atherosclerosis development in the offspring of ApoE−/− mice. The authors observed that perinatal hypercholesterolemia exacerbates atherosclerosis in their offspring by epigenetically modulating several genes implicated in the metabolism of trimethylamine-N-oxide and bile acids via DNA methylation (Trenteseaux, et al, 2017).…”

Section: Trans-generational Inheritance and Trained Immunitymentioning

confidence: 99%

Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics

Kamato

Little

et al. 2019

Pharmacology & Therapeutics

122

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Atherosclerosis, the principal cause of cardiovascular death worldwide, is a pathological disease characterized by fibro-proliferation, chronic inflammation, lipid accumulation, and immune disorder in the vessel wall. As the atheromatous plaques develop into advanced stage, the vulnerable plaques are prone to rupture, which causes acute cardiovascular events, including ischemic stroke and myocardial infarction. Emerging evidence has suggested that atherosclerosis is also an epigenetic disease with the interplay of multiple epigenetic mechanisms. The epigenetic basis of atherosclerosis has transformed our knowledge of epigenetics from an important biological phenomenon to a burgeoning field of cardiovascular research. Here, we provide a systematic and up-to-date overview of the current knowledge of three distinct but interrelated epigenetic processes (including DNA methylation, histone methylation/acetylation, and noncoding RNAs), in atherosclerotic plaque development and instability. Mechanistic and conceptual advances in understanding the biological roles of various epigenetic modifiers in regulating gene expression and functions of endothelial cells (vascular homeostasis, leukocyte adhesion, endothelial-mesenchymal transition, angiogenesis, and mechanotransduction), smooth muscle

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“…These findings concurred with the results of a previous report demonstrating the deleterious effects of FMO3 expression in glucose tolerance in liver-specific insulin receptor knockout mice [ 92 ]. Additionally, another recent study demonstrated that maternal hypercholesterolemia exacerbates the development of atherosclerosis with a positive association of aortic lesion size with both TMAO levels and increased FMO3 mRNA expression [ 93 ]. Overall, these data strongly indicate a role for FMO3 in modulating lipid and glucose homeostasis in vivo in a dose-dependent manner and, in some cases, independently of TMA/TMAO formation.…”

Section: The Physiological Interaction Between Tmao and Hdl In Thementioning

confidence: 99%

Trimethylamine N-Oxide: A Link among Diet, Gut Microbiota, Gene Regulation of Liver and Intestine Cholesterol Homeostasis and HDL Function

Canyelles

Tondo

Cedó

et al. 2018

IJMS

146

120

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Recent evidence, including massive gene-expression analysis and a wide-variety of other multi-omics approaches, demonstrates an interplay between gut microbiota and the regulation of plasma lipids. Gut microbial metabolism of choline and l-carnitine results in the formation of trimethylamine (TMA) and concomitant conversion into trimethylamine-N-oxide (TMAO) by liver flavin monooxygenase 3 (FMO3). The plasma level of TMAO is determined by the genetic variation, diet and composition of gut microbiota. Multiple studies have demonstrated an association between TMAO plasma levels and the risk of atherothrombotic cardiovascular disease (CVD). We aimed to review the molecular pathways by which TMAO production and FMO3 exert their proatherogenic effects. TMAO may promote foam cell formation by upregulating macrophage scavenger receptors, deregulating enterohepatic cholesterol and bile acid metabolism and impairing macrophage reverse cholesterol transport (RCT). Furthermore, FMO3 may promote dyslipidemia by regulating multiple genes involved in hepatic lipogenesis and gluconeogenesis. FMO3 also impairs multiple aspects of cholesterol homeostasis, including transintestinal cholesterol export and macrophage-specific RCT. At least part of these FMO3-mediated effects on lipid metabolism and atherogenesis seem to be independent of the TMA/TMAO formation. Overall, these findings have the potential to open a new era for the therapeutic manipulation of the gut microbiota to improve CVD risk.

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Perinatal Hypercholesterolemia Exacerbates Atherosclerosis Lesions in Offspring by Altering Metabolism of Trimethylamine-N-Oxide and Bile Acids

Abstract: Our findings suggest that maternal hypercholesterolemia may exacerbate the development of atherosclerosis in female offspring by affecting metabolism of trimethylamine-N-oxide and bile acids. These data could be explained by epigenetic alterations.

Cited by 38 publications

References 48 publications

Impact of Gut Microbiota and Diet on the Development of Atherosclerosis in Apoe ^−/− Mice

Impact of Gut Microbiota and Diet on the Development of Atherosclerosis in Apoe ^−/− Mice

Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics

Trimethylamine N-Oxide: A Link among Diet, Gut Microbiota, Gene Regulation of Liver and Intestine Cholesterol Homeostasis and HDL Function

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Perinatal Hypercholesterolemia Exacerbates Atherosclerosis Lesions in Offspring by Altering Metabolism of Trimethylamine-N-Oxide and Bile Acids

Abstract: Our findings suggest that maternal hypercholesterolemia may exacerbate the development of atherosclerosis in female offspring by affecting metabolism of trimethylamine-N-oxide and bile acids. These data could be explained by epigenetic alterations.

Cited by 38 publications

References 48 publications

Impact of Gut Microbiota and Diet on the Development of Atherosclerosis in Apoe −/− Mice

Impact of Gut Microbiota and Diet on the Development of Atherosclerosis in Apoe −/− Mice

Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics

Trimethylamine N-Oxide: A Link among Diet, Gut Microbiota, Gene Regulation of Liver and Intestine Cholesterol Homeostasis and HDL Function

Contact Info

Product

Resources

About

Impact of Gut Microbiota and Diet on the Development of Atherosclerosis in Apoe ^−/− Mice

Impact of Gut Microbiota and Diet on the Development of Atherosclerosis in Apoe ^−/− Mice