Trymethylamine-N-oxide, a gut-derived metabolite, induces myofibroblastic activation of valvular interstitial cells through endoplasmic reticulum stress.

ABSTRACT: Calcific aortic valve disease currently lacks effective treatments beyond surgical valve replacement, due to an incomplete understanding of its pathogenesis. Emerging evidence suggests that the gut microbiome influences cardiovascular health through the production of metabolites derived from dietary components. Among them, trimethylamine-N-oxide (TMAO) has been identified as a potential causal factor for several cardiovascular conditions. However, its role in the development of aortic valve disease remains poorly understood. This study sought to investigate the impact of TMAO on valvular interstitial cells (VICs), the most abundant cell type in the aortic valve. Here, we demonstrate that TMAO activates VICs towards a myofibroblastic profibrotic phenotype. Using an in vitro protocol

SUBMITTER: Sudi S 

PROVIDER: S-EPMC11839121 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature