Differential Mechanisms of Soybean-Derived ACE2-Activating Peptides IVPQ and IAVPT in ACE2-Mediated Endothelial Protection

This study aimed to investigate the modulatory effects of soybean-derived peptides IVPQ and IAVPT, which were initially identified as potent ACE2-activating peptides, on Ang II-induced endothelial dysfunction in human umbilical vein endothelial cells (HUVECs) and the underlying mechanisms via ACE2 activation. IVPQ and IAVPT ameliorated Ang II-induced malignant migration and NO reduction in HUVECs via the activation of the ACE2/Ang-(1-7)/MasR axis, resulting in Ang II degradation and decreased Ang II signaling. These protective effects were attenuated by ACE2 knockdown to different degrees, which was possibly due to different mechanisms of activating ACE2, where IAVPT directly activated ACE2 at a concentration of 1.0 × 10^-4 M and IVPQ upregulated ACE2 likely through effects on ACE2 mRNA stability. These results contributed to our understanding of the mechanism of ACE2-activating peptides regulating endothelial function.