Endothelial TMAO Transporter 1 (ETT1)

Endothelial TMAO Transporter 1 (ETT1) is a recently identified solute carrier protein that mediates the uptake of trimethylamine N-oxide (TMAO) into vascular endothelial cells. TMAO is a metabolite produced by gut bacteria from dietary precursors like choline and carnitine, and its elevated systemic levels are strongly associated with an increased risk of cardiovascular diseases. ETT1 is upregulated in inflammatory-activated endothelial cells, particularly in the myocardium, where it facilitates the accumulation of TMAO. This intracellular accumulation leads to the activation of the NLRP3 inflammasome, increased expression of adhesion molecules such as E-selectin and ICAM-1, and the induction of endothelial-to-mesenchymal transition (EndMT). By promoting these pathological processes, ETT1 plays a critical role in the development of endothelial dysfunction and atherosclerosis. Targeting ETT1 with small molecule inhibitors or RNA interference represents a novel therapeutic strategy to mitigate the detrimental effects of diet-derived TMAO on the cardiovascular system.

Other names

ETT1Endothelial Trimethylamine N-oxide Transporter 1

ETT1 facilitates the intracellular uptake of gut-microbiota-derived trimethylamine N-oxide (TMAO) into endothelial cells. Once inside, TMAO triggers pro-inflammatory signaling pathways, including the activation of the NLRP3 inflammasome and the induction of endothelial-to-mesenchymal transition (EndMT), which contributes to vascular wall remodeling and atherosclerotic plaque formation.