Milk-derived tripeptides IPP (Ile-Pro-Pro) and VPP (Val-Pro-Pro) differentially modulate angiotensin II effects on vascular smooth muscle cells.

Hyperactivity of the Renin-Angiotensin System (RAS) is a hallmark of hypertension. Angiotensin II (AngII), the active component of RAS, not only promotes vasoconstriction but also contributes to proliferation, inflammation and oxidative stress in vascular smooth muscle cells (VSMC) that predispose to atherosclerosis. Milk derived bioactive peptides IPP (Ile-Pro-Pro) and VPP (Val-Pro-Pro) exert anti-hypertensive effects through RAS modulation. Here we evaluated the ability of these peptides to attenuate the effects of AngII on cultured VSMC. We found that VPP significantly inhibited AngII induced cell proliferation, inflammation and oxidative stress while IPP only showed anti-oxidant actions. Both peptides abolished AngII mediated activation of pro-inflammatory nuclear factor kappa B (NF-κB) pathway but only VPP could attenuate activation of extracellular signal regulated kinases (ERK) 1/2. These results demonstrate differential modulation of AngII actions on VSMC by anti-hypertensive milk peptides and indicate the potential for VPP in mitigating the vascular complications of hypertension.