Soybean-Derived Antihypertensive Peptide LSW (Leu–Ser–Trp) Antagonizes the Damage of Angiotensin II to Vascular Endothelial Cells through the Trans-vesicular Pathway

An emerging inference is that vascular cells transfer their biological cargo to recipient cells by secretion of extracellular vesicles (EVs). This study explored the effects of EVs produced from VSMCs with Ang II (EVs-A) or LSW + Ang II on HUVECs. The EVs-A increase ROS production, activate inflammation, and upregulate the expression of adhesion molecules. Among the EVs-A, miR-22, miR-143, miR-144, and miR-155 were significantly downregulated, while VSMCs pre-incubated with LSW could produce improved EVs. RNA sequencing revealed differential expression of genes associated with endothelial dysfunction, including the TNF signaling pathway, NOD-like receptor signaling pathway, NF-κB signaling pathway, and fluid shear stress and atherosclerosis pathway. Finally, we found that LSW could improve endothelial function by repairing the expression of miRNAs in VSMCs. It also suggests a potential mechanism for the injury action of endogenous peptide Ang II and protective effects of exogenous peptide LSW on vascular endothelial cells.