School of Food Science and Engineering, South China University of Technology, Guangzhou 510640, P.R. China.
Guangdong Food Green Processing and Nutrition Regulation Technologies Research Center, Guangzhou 510640, P.R. China.
J Agric Food Chem. 2023 Aug 9;71(31):11957-11969. doi: 10.1021/acs.jafc.3c03013. Epub 2023 Jul 27.
Angiotensin-converting enzyme 2 (ACE2) is a counterregulator against ACE by converting angiotensin II (Ang II) to Ang-(1-7), and its down-regulation leads to endothelial dysfunction in the vascular system. In the present study, we investigated the effects of soybean protein isolate hydrolysate (SPIH) on Ang II-induced endothelial dysfunction with its underlying mechanisms via ACE2 activation in human umbilical vein endothelial cells (HUVECs). We further screened potential ACE2 activating peptides by peptidomics analysis combined with bioinformatics tools. Results showed that SPIH remarkably attenuated Ang II-induced cell migration from 129 to 92%, decreased the ROS level from 2.22-fold to 1.45-fold, and increased NO concentration from 31.4 ± 0.7 to 43.7 ± 0.1 μM in HUVECs. However, these beneficial effects were reversed by ACE2 inhibitor MLN-4760 to a certain extent, indicating the modulation of ACE2. Further results revealed that SPIH (1 mg/mL) significantly increased the expression and activity of ACE2 and two novel ACE2 activating peptides with different mechanisms were explored from SPIH. IVPQ and IAVPT (50 μM) enhanced ACE2 activity, and only IVPQ (50 μM) increased ACE2 protein expression in HUVECs. These findings furthered our understanding of the antihypertensive mechanism of SPIH mediating the ACE2 activation on vascular endothelium.
血管紧张素转换酶 2（ACE2）通过将血管紧张素 II（Ang II）转化为 Ang-(1-7) 来对抗 ACE，其下调导致血管系统内皮功能障碍。在本研究中，我们通过人脐静脉内皮细胞（HUVEC）中 ACE2 的激活，研究了大豆蛋白分离物水解物（SPIH）对 Ang II 诱导的内皮功能障碍的影响及其潜在机制。我们进一步通过肽组学分析结合生物信息学工具筛选潜在的 ACE2 激活肽。结果表明，SPIH 显著抑制 Ang II 诱导的细胞迁移，从 129%降至 92%，降低 ROS 水平，从 2.22 倍降至 1.45 倍，增加 NO 浓度，从 31.4±0.7μM 增至 43.7±0.1μM。然而，这些有益作用在一定程度上被 ACE2 抑制剂 MLN-4760 逆转，表明 ACE2 的调节作用。进一步的结果表明，SPIH（1mg/mL）显著增加 ACE2 的表达和活性，并从 SPIH 中探索出两种具有不同机制的新型 ACE2 激活肽。IVPQ 和 IAVPT（50μM）增强 ACE2 活性，只有 IAVPT（50μM）增加 HUVEC 中 ACE2 蛋白表达。这些发现进一步加深了我们对 SPIH 通过激活 ACE2 对血管内皮的降压机制的理解。
