Chicken Muscle-Derived ACE2 Upregulating Peptide VVHPKESF Inhibits Angiotensin II-Stimulated Inflammation in Vascular Smooth Muscle Cells via the ACE2/Ang (1–7)/MasR Axis

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.

Angiotensin-Converting Enzyme 2 Activation Is Not a Common Feature of Angiotensin-Converting Enzyme Inhibitory Peptides

“…At the concentration of 50 μM, cell viability was not affected by peptides (Figure ). The dose of peptides was selected based on our previous studies. ,, Among the 20 peptides tested, 12 peptides, IRY, IQY, HHL, IKW, IRP, VRF, LRP, VKK, ARF, LKP, MAW, and PRY, could significantly increase ACE2 protein level in cells (Figure ). Among them, IQY and MAW showed the highest increase in ACE2 protein level, similar to that of IRW in A7r5 cells …”

“…Activation of ACE2 and, more specifically, the ACE2/Ang (1–7)/MasR axis represents an emerging strategy to treat hypertension, aortic hypertrophy, cardiac remodeling, and heart failure . ACE2 can be activated via two mechanisms, including increased ACE2 enzymatic activity and/or enhanced ACE2 transcription. , One chicken muscle-derived peptide VVHPKESF could activate ACE2 which reduced Ang II-induced vascular inflammation via the ACE2/Ang (1–7)/MasR axis; it also lowered BP in SHR significantly via oral administration. − Likewise, pea protein-derived peptide AKSLSDRFSY and its fragments (LSDRFS and SDRFSY) also showed ACE2 activating (ACE2a) activity in cells . In contrast with numerous reports on food-derived ACEi peptides, there is scarce information on ACE2a peptides.…”

Chicken Muscle Protein‐Derived Peptide VVHPKESF Reduces TNFα‐Induced Inflammation and Oxidative Stress by Suppressing TNFR1 Signaling in Human Vascular Endothelial Cells

“…[19] Dosage Information: Peptides were added into the cultured media to treat the cells at the concentration of 25-100 μM for different period of time (within 24 h), based on previous studies. [19,63] Specific treatment doses and periods of time were described in their respective assays.…”

Soybean-Derived Tripeptide Leu–Ser–Trp (LSW) Protects Human Vascular Endothelial Cells from TNFα-Induced Oxidative Stress and Inflammation via Modulating TNFα Receptors and SIRT1

“…After treatment, cells were first washed with cold PBS and were then lysed using boiling Laemmli’s buffer (containing 50 mM DTT and 0.2% Triton-X-100). Lysates were loaded and run in a 9% separating gel, followed by being transferred onto a nitrocellulose membrane, blocked with bovine serum albumin, and incubated with primary and secondary antibodies [ 18 ]. The effect of LSW treatment on inflammatory proteins and TNFα receptors was studied after 6 h of TNFα stimulation.…”