Chicken Muscle-Derived ACE2 Upregulating Peptide VVHPKESF Inhibits Angiotensin II-Stimulated Inflammation in Vascular Smooth Muscle Cells <i>via</i> the ACE2/Ang (1–7)/MasR Axis
Hongbing Fan, Wang Liao, Sandra T. Davidge, Jianping Wu
Abstract
This study aimed to evaluate the modulatory effects of four chicken muscle-derived peptides [VRP, LKY, VRY, and VVHPKESF (V–F)] on angiotensin II (Ang II)-induced inflammation in rat vascular smooth muscle A7r5 cells. Only V–F could significantly attenuate Ang II-stimulated inflammation via the inhibition of NF-κB and p38 MAPK signaling, being dependent on the Mas receptor (MasR) not on the Ang II type 1 or type 2 receptor (AT1R or AT2R). V–F accelerated Ang II degradation by enhancing cellular ACE2 activity, which was due to ACE2 upregulation other than a direct ACE2 activation. These findings demonstrated that V–F ameliorated Ang II-induced inflammation in A7r5 cells via the ACE2/Ang (1–7)/MasR axis. Three peptide metabolites of V–F─VHPKESF, PKESF, and SF─were identified but were not considered major contributors to V–F’s bioactivity. The regulation of peptide V–F on vascular inflammation supported its functional food or nutraceutical application in the prevention and treatment of hypertension and cardiovascular diseases.