J Agric Food Chem. 2018 Oct 31;66(43):11330-11336. doi: 10.1021/acs.jafc.8b03501. Epub 2018 Oct 22.
Angiotensin converting enzyme 2 (ACE2) plays beneficial roles in the renin angiotensin aldosterone system. Our previous studies indicated that egg white-derived antihypertensive peptide IRW (Ile-Arg-Trp) could upregulate ACE2 mRNA level in mesenteric artery of spontaneously hypertensive rats (SHRs), suggesting the potential of IRW as an in vivo ACE2 activator. In this study, the effects of IRW on activity and protein expression of ACE2 were investigated. Results indicated that IRW activated human recombinant ACE2 with an EC value of 7.24 × 10 M. In rat aortic vascular smooth muscle cell line A7r5 cells, IRW treatment (50 μM) significantly increased the expression and activity of ACE2. Oral administration of IRW to SHRs upregulated ACE2 protein levels in kidney and aorta. Molecular docking study suggested that IRW might activate ACE2 through interaction with the subdomain I near the active site through hydrogen bonds. Overall, this study established IRW as the first food-derived ACE2 activating peptide.
血管紧张素转化酶 2（ACE2）在肾素-血管紧张素-醛固酮系统中发挥有益作用。我们之前的研究表明，蛋清来源的降压肽 IRW（Ile-Arg-Trp）可上调自发性高血压大鼠（SHR）肠系膜动脉中的 ACE2 mRNA 水平，提示 IRW 作为体内 ACE2 激活剂的潜力。在这项研究中，研究了 IRW 对 ACE2 活性和蛋白表达的影响。结果表明，IRW 以 EC 值为 7.24×10 M 激活人重组 ACE2。在大鼠主动脉血管平滑肌细胞系 A7r5 细胞中，IRW 处理（50 μM）显著增加 ACE2 的表达和活性。IRW 口服给予 SHRs 可上调肾脏和主动脉中的 ACE2 蛋白水平。分子对接研究表明，IRW 可能通过氢键与活性部位附近的子域 I 相互作用来激活 ACE2。总的来说，这项研究确立了 IRW 为首个食物来源的 ACE2 激活肽。
