Endothelial monocarboxylate transporter 1 drives atherosclerosis via a lactate/NADH/CtBP-mediated transrepression pathway.

ABSTRACT: The accumulation of lactate in tissue microenvironments is associated with atherosclerosis, but its precise role in atherogenesis remains largely unknown. This study demonstrated that lactate accumulation in aortic tissues and blood is correlated with increased monocarboxylate transporter 1 (Mct1) expression in endothelial cells (ECs) within atherosclerotic plaques. Lactate uptake via Mct1 triggers an inflammatory response in ECs. The administration of endothelial-targeting nanoparticles containing siRNA against Mct1 reduces endothelial inflammation and atherogenesis in Apoe^-/- mice. Mechanistic studies revealed that the conversion of lactate to pyruvate, along with NADH production and oligomerization of the NADH-sensitive transcriptional corepressor C-terminal bin

SUBMITTER: Li Z 

PROVIDER: S-EPMC11822463 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature