Revisiting the mechanisms of ACE inhibitory peptides from food proteins

Angiotensin converting enzyme (ACE) is a key enzyme in the renin angiotensin system (RAS) responsible for conversion of angiotensin (Ang) I into Ang II, a vasoconstrictor leading to elevated blood pressure. ACE inhibitory (ACEi) peptides derived from food proteins have shown potential in the prevention and management of hypertension. Although most ACEi peptides were characterized based on in vitro ACEi activity, a relationship between ACE inhibition and physiological antihypertensive effect is not apparent, indicating the involvement of other mechanisms of action. This paper focuses on emerging antihypertensive mechanisms of ACEi peptides. As an alternate arm of the classic RAS, ACE2 cleaves Ang II into Ang (1–7) and thus counterbalances the harmful effects of Ang II. Endothelial dysfunction is now recognized as an early feature in the pathophysiology of metabolic syndrome and cardiovascular disorders including hypertension; endothelial dysfunction, vascular oxidative stress and inflammation are interplayed. Future perspectives on mechanistic study of ACEi peptides are forecasted. Apart from classic ACE inhibition, emerging evidence suggests that food peptides can exert antihypertensive activity through upregulation of ACE2 (an ACE homologue that counterbalances the detrimental effect of elevated ACE), improvement of endothelial function, as well as reduced vascular oxidation and inflammation. Future research is expected to look into the effects of bioaccessibility, bioavailability, stability and reactivity of the peptides with food and gut matrices, as well as the gut microbiota, on blood pressure reduction.