Lupin peptides: novel bi-functional inhibitors of PCSK9, a new target for the cardiovascular disease risk reduction

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been recently identified as a new target for hypercholesterolemia treatment. We have demonstrated that peptides, deriving from lupin protein hydrolysis and absorbable at intestinal level, are able to modulate the PCSK9 target with a dual mechanism of action. Lupin peptides reduce PCSK9 production and secretion through a decrease of HNF1-alpha in HepG2 cells and an absorbed lupin peptide is able to inhibit the protein-protein interaction between PCSK9 and the LDL receptor with an IC50 value equal to 1.6±0.33 μM. Interestingly, in mild hypercholesterolemic subjects, which had consumed lupin protein (30 g/day) for 4 weeks, the final circulating PCSK9 level had been reduced by 8.5% versus baseline value. For the first time, we have provided evidences that lupin peptides may modulate PCSK9, contributing to explain the beneficial effects observed in clinical studies and opening a new area of investigation on plant proteins.