Tripeptide Leu-Ser-Trp Regulates the Vascular Endothelial Cells Phenotype Switching by Mediating the Vascular Smooth Muscle Cells-Derived Small Extracellular Vesicles Packaging of miR-145

Tripeptide LSW, initially identified as a potent ACE inhibitory peptide from soybean protein, was recently reported to exert a protective effect against angiotensin II-induced endothelial dysfunction via extracellular vesicles (EVs). However, the molecular mechanisms, especially in lipid accumulation-induced atherosclerosis, still remain unclear. The study aimed to investigate whether the protective effects of LSW against endothelial dysfunction on vascular endothelial cells (VECs) was via vascular smooth muscle cells (VSMCs)-derived miRNA-145 packaged in EVs. The miRNA-145 was concentrated in EVs from LSW-treated VSMCs (LEVs), internalized into the HVUECs, and targeted the programmed cell death protein 4 (PDCD4) expression of HUVECs. Oxidized low-density lipoprotein (oxLDL) was applied to induce endothelial dysfunction in HUVECs; oxLDL-induced endothelial dysfunction in HUVECs was attenuated by PDCD4 knockout or LEVs incubation. The results of this study suggested a novel function of LSW as a regulator on the functional EVs from vascular cells in the oxLDL-induced atherosclerotic model.