Impact of Soy β-Conglycinin Peptides on PCSK9 Protein Expression in HepG2 Cells

Background: Dyslipidaemias, particularly elevated plasma low-density lipoprotein cho- lesterol (LDL-C) levels, are major risk factors for cardiovascular disease (CVD). Besides pharmaco- logical approaches, a nutritional strategy for CVD prevention has gained increasing attention. Among functional foods, the hypocholesterolemic properties of soy are driven by a stimulation of LDL-receptor (LDL-R) activity. Aim: To characterize the effect of two soy peptides, namely, β- conglycinin-derived YVVNPDNDEN and YVVNPDNNEN on the expression of proprotein con- vertase subtilisin/kexin type 9 (PCSK9), one of the key-regulators of the LDL-R. Methods: PCSK9 promoter activity (luciferase assay), PCSK9 protein expression (WB) and secretion (ELISA), PCSK9 interaction with LDL-R (binding assay) and human HepG2 cells were the objects of this investiga- tion. Results: Treatment with YVVNPDNNEN peptide has led to a rise in PCSK9 gene expression (90.8%) and transcriptional activity (86.4%), and to a decrement in PCSK9 intracellular and secreted protein (−42.9%) levels. YVVNPDNNEN peptide reduced the protein expression of transcriptional factor HNF1α. Most changes driven by YVVNPDNDEN peptide were not statistically significant. Neither peptide inhibited the PCSK9–LDLR interaction. Conclusions: Although sharing a common effect on LDL-R levels through the inhibition of 3-hydroxy-3-methylglutaryl CoA reductase activity, only the YVVNPDNNEN peptide has an additional mechanism via the downregulation of PCSK9 protein levels.