TMAO Upregulates Members of the miR-17/92 Cluster and Impacts Targets Associated with Atherosclerosis

被引：15

作者：

Diez-Ricote, Laura ^{[1
]}

Ruiz-Valderrey, Paloma ^{[1
]}

Mico, Victor ^{[1
]}

Blanco, Ruth ^{[1
,2
]}

Tome-Carneiro, Joao ^{[3
]}

Davalos, Alberto ^{[3
]}

Ordovas, Jose M. ^{[1
,4
]}

Daimiel, Lidia ^{[1
]}

机构：

[1] UAM CSIC, IMDEA Food, Precis Nutr & Obes Program, Nutr Control Epigenome Grp, Madrid 28049, Spain

[2] Biosearch Life Co, Res & Dev Dept, Madrid 28031, Spain

[3] UAM CSIC, IMDEA Food, Precis Nutr & Cardiometab Hlth Program, Epigenet Lipid Metab Grp, Madrid 28049, Spain

[4] Tufts Univ, JM USDA Human Nutr Res Ctr Aging, Nutr & Genom Lab, Boston, MA 02111 USA

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2022年 / 23卷 / 20期

关键词：

cardiovascular disease; TMAO; microRNAs; atherosclerosis; inflammation; PLASMINOGEN-ACTIVATOR INHIBITOR-1; MICRORNA CLUSTER; GUT MICROBIOTA; RED MEAT; INFLAMMATION; EXPRESSION; METABOLISM; APOPTOSIS; HEALTHY; PAI-1;

D O I：

10.3390/ijms232012107

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Atherosclerosis is a hallmark of cardiovascular disease, and lifestyle strongly impacts its onset and progression. Nutrients have been shown to regulate the miR-17/92 cluster, with a role in endothelial function and atherosclerosis. Choline, betaine, and L-carnitine, found in animal foods, are metabolized into trimethylamine (TMA) by the gut microbiota. TMA is then oxidized to TMAO, which has been associated with atherosclerosis. Our aim was to investigate whether TMAO modulates the expression of the miR-17/92 cluster, along with the impact of this modulation on the expression of target genes related to atherosclerosis and inflammation. We treated HepG-2 cells, THP-1 cells, murine liver organoids, and human peripheral mononuclear cells with 6 mu M of TMAO at different timepoints. TMAO increased the expression of all analyzed members of the cluster, except for miR-20a-5p in murine liver organoids and primary human macrophages. Genes and protein levels of SERPINE1 and IL-12A increased. Both have been associated with atherosclerosis and cardiovascular disease (CDVD) and are indirectly modulated by the miR-17-92 cluster. We concluded that TMAO modulates the expression of the miR-17/92 cluster and that such modulation could promote inflammation through IL-12A and blood clotting through SERPINE1 expression, which could ultimately promote atherosclerosis and CVD.

引用

页数：10