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

Chiara Macchi,Alberto Corsini,Carmen Lammi,Anna Arnoldi,Cesare R Sirtori,Nicola Ferri,Maria Francesca Greco,Massimiliano Ruscica,Paolo Magni

doi:10.3390/nu14010193

Abstract

Background: Dyslipidaemias, particularly elevated plasma low-density lipoprotein cholesterol (LDL-C) levels, are major risk factors for cardiovascular disease (CVD). Besides pharmacological 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 convertase 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 investigation. 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.

Highlights

Dyslipidaemias are plasma lipid alterations frequently associated with clinical conditions affecting the arterial system
Staining treated cells with FITC annexin V and PI did not reveal any difference in the percentage of live cells between controls and HepG2 treated with YVVNPDNDEN, or YVVNPDNNEN
Similar conclusions were reached in the case of simvastatin, which was used as a positive control of proprotein convertase subtilisin/kexin type 9 (PCSK9) activation throughout the manuscript

Summary

Introduction

Dyslipidaemias are plasma lipid alterations frequently associated with clinical conditions affecting the arterial system. Elevated levels of low-density lipoprotein cholesterol (LDL-C) represent one of the major risk factors for cardiovascular disease (CVD) [1]. Several “functional foods”, i.e., food items providing additional health benefit beyond energy production, have shown a clear activity on LDL-C levels. Among these are plant proteins, e.g., soybean proteins [4], providing an excellent source of protein, dietary fibres, and phytochemicals. Dyslipidaemias, elevated plasma low-density lipoprotein cholesterol (LDL-C) levels, are major risk factors for cardiovascular disease (CVD). 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%)

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