title: 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.
authors.affiliation: Nanotechnology Research Center, Department of Medical Biotechnology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Amir Abbas
authors.initials: AA
authors.lastname: Momtazi
authors.affiliation: Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz, Zeromskiego 113, Lodz, Poland; Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Banach
authors.affiliation: Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Medicine, University of Perugia, Perugia, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Pirro
authors.affiliation: Second Propedeutic Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, Hippocration Hospital, Thessaloniki, Greece.
authors.forename: Niki
authors.initials: N
authors.lastname: Katsiki
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran; Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia. Electronic address: sahebkara@mums.ac.ir.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Sahebkar
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008078:Cholesterol, LDL / Q000097:blood / Q000378:metabolism; D019587:Dietary Supplements / Q000032:analysis; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000091362:PCSK9 Inhibitors; D000071449:Proprotein Convertase 9 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000091362:PCSK9 Inhibitors; D000071449:Proprotein Convertase 9
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