Regulation of PCSK9 by nutraceuticals

Abstract

PCSK9 (proprotein convertase subtilisin kexin type 9) is a liver secretory enzyme that regulates plasma low-density lipoprotein (LDL) cholesterol (LDL-C) levels through modulation of LDL receptor (LDLR) density on the surface of hepatocytes. Inhibition of PCSK9 using monoclonal antibodies can efficiently lower plasma LDL-C, non-high-density lipoprotein cholesterol and lipoprotein (a). PCSK9 inhibition is also an effective adjunct to statin therapy; however, the cost-effectiveness of currently available PCSK9 inhibitors is under question. Nutraceuticals offer a safe and cost-effective option for PCSK9 inhibition. Several nutraceuticals have been reported to modulate PCSK9 levels and exert LDL-lowering activity. Mechanistically, those nutraceuticals that inhibit PCSK9 through a SREBP (sterol-responsive element binding protein)-independent pathway can be more effective in lowering plasma LDL-C levels compared with those inhibiting PCSK9 through the SREBP pathway. The present review aims to collect available data on the nutraceuticals with PCSK9-inhibitory effect and the underlying mechanisms.

Keywords: 3-hydroxy-3-methylglutaryl-coenzyme A; ALA; APMF; ASCVD; ApoB; ApoER2; CGN; COMIT; DHA; DPA; Docosapentaenoic acid; EGF-A; EPA; ER; FH; GK; HMG-CoA; HNF1; HeFH; LDL; LDL-C; LPS; PCSK9; alpha-linolenic acid; apolipoprotein B; apolipoprotein E receptor2; aqueous extract of PM fruit;; atherosclerotic cardiovascular disease; berberine; canola oil multicenter intervention trial; cerebellar granule neurons; curcumin; docosahexaenoic acid; eicosapentaenoic acid; endoplasmic reticulum; epidermal growth factor-like repeat A; familial hypercholesterolemia; glucokinase; hepatocyte nuclear factor1; heterozygous familial hypercholesterolemia; hyperlipidemia; lipopolysaccharide; low-density lipoprotein; phytochemical.