Egg White-Derived Tripeptide IRW (Ile-Arg-Trp) Is an Activator of Angiotensin Converting Enzyme 2

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 EC₅₀ value of 7.24 × 10^-5 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.