Identification and Screening of Potential ACE2 Activating Peptides from Soybean Protein Isolate Hydrolysate against Ang II-Induced Endothelial Dysfunction

作者：Zhou, Minzhi; Song, Tianyuan; Li, Wen; Huang, Mingtao; Zheng, Lin^*; Zhao, Mouming^*

来源：Journal of Agricultural and Food Chemistry, 2023, 71(31): 11957-11969.

DOI：10.1021/acs.jafc.3c03013

• soybean protein isolate hydrolysate
• ACE2
• angiotensin II
• endothelial dysfunction
• ACE2 activatingpeptide
• peptidomics
• bioinformatics

Angiotensin-converting enzyme 2 (ACE2) is a counterregulatoragainstACE by converting angiotensin II (Ang II) to Ang-(1-7), andits down-regulation leads to endothelial dysfunction in the vascularsystem. In the present study, we investigated the effects of soybeanprotein isolate hydrolysate (SPIH) on Ang II-induced endothelial dysfunctionwith its underlying mechanisms via ACE2 activation in human umbilicalvein endothelial cells (HUVECs). We further screened potential ACE2activating peptides by peptidomics analysis combined with bioinformaticstools. Results showed that SPIH remarkably attenuated Ang II-inducedcell migration from 129 to 92%, decreased the ROS level from 2.22-foldto 1.45-fold, and increased NO concentration from 31.4 & PLUSMN; 0.7to 43.7 & PLUSMN; 0.1 & mu;M in HUVECs. However, these beneficial effectswere reversed by ACE2 inhibitor MLN-4760 to a certain extent, indicatingthe modulation of ACE2. Further results revealed that SPIH (1 mg/mL)significantly increased the expression and activity of ACE2 and twonovel ACE2 activating peptides with different mechanisms were exploredfrom SPIH. IVPQ and IAVPT (50 & mu;M) enhanced ACE2 activity, andonly IVPQ (50 & mu;M) increased ACE2 protein expression in HUVECs.These findings furthered our understanding of the antihypertensivemechanism of SPIH mediating the ACE2 activation on vascular endothelium.