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The gut microbe-derived metabolite trimethylamine-N-oxide induces aortic valve fibrosis via PERK/ATF-4 and IRE-1α/XBP-1s signaling in vitro and in vivo
Gut microbe chemical trimethylamine-N-oxide may cause aortic valve scarring through specific cell stress signals in lab and animal studies
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Abstract
Diseased aortic valves produced greater levels of ATF-4, XBP-1, collagen Ⅰ, and TGF-β1 after TMAO stimulation.
- TMAO may activate the PERK/ATF-4 and IRE-1α/XBP-1s signaling pathways, which are associated with cardiovascular fibrosis.
- Inhibition and silencing of these signaling pathways resulted in enhanced suppression of TMAO-induced fibrogenic activity in diseased aortic valve cells.
- Mice given dietary choline supplementation exhibited substantially increased TMAO levels and aortic valve fibrosis.
- Treatment with an inhibitor of trimethylamine formation reduced aortic valve fibrosis in mice on a high-choline diet.
- A high-choline and high-fat diet is associated with remodeling of the gut microbiota in mice.
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