Impact of TMAO-triggered EndMT and its derived extracellular vesicles on vascular smooth muscle cell phenotypic changes and calcification

Abstract

Background and Aims: Cardiovascular diseases (CVDs) are the leading global cause of death, with vascular calcification (VC) as a critical predictor, particularly in atherosclerosis. VC involves calcium phosphate deposition in blood vessels, driven by vascular smooth muscle cell (VSMC) transdifferentiation into osteoblast-like cells under inflammatory and mineral imbalance conditions. Endothelial cells (ECs) also contribute to VC through endothelial-to-mesenchymal transition (EndMT), producing osteogenic progenitors. Trimethylamine-N-oxide (TMAO), a gut microbiota-derived molecule, promotes endothelial dysfunction and inflammation. The role of EC-derived exosomes in influencing VSMC behavior and VC progression still needs to be explored. We aim to determine whether TMAO treatment induces EndMT in endothelial cells. In addition, we are assessing the impact of exosomes derived from TMAO-treated endothelial cells on the differentiation and calcification of VSMCs.