Tripeptides Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) Regulate the Proliferation and Migration of Vascular Smooth Muscle Cells by Interfering Ang II-Induced Human Umbilical Vein Endothelial Cells Derived EVs Delivering RNAs to VSMCs in the Co-culture Model

Angiotensin II (Ang II), a vasoactive factor in the renin–angiotensin–aldosterone system (RAAS), can regulate vasoconstriction and promote multiple vascular diseases. In this study, the effects of potent antihypertensive peptide Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP) on the proliferation and migration of vascular smooth muscle cells (VSMCs) by extracellular vesicles (EVs) from vascular endothelial cells (VECs) were studied using a cell co-culture model. The VEC-derived EVs were isolated, characterized, and investigated. The present study demonstrated that the EVs from Ang II-induced VECs could promote proliferation, migration, and inflammatory factors (IL-6 increased to 40.75 ± 4.33 pg/mL and IL-1β increased to 28.62 ± 5.42 pg/mL) generation of VSMCs, VPP and IPP exerted discrepant inhibitory effects on this pathway. The EVs with RNase treatment lost the effects on VSMCs, indicating that the RNAs packed into vesicles may be a critical component. These results implied that VPP and IPP could alleviate Ang II-induced vascular dysfunction by modulating the EV-mediated transmission of RNAs between VECs and VSMCs.