title: PCSK9 and its modulation.
abstract: Proprotein convertase subtilisin/kexin type 9 (PCSK9), a newly-recognized protein, plays a key role in regulating cholesterol homeostasis. PCSK9 reduces hepatic low-density lipoprotein receptors (LDLRs) thereby increasing LDL-cholesterol (LDL-C). Recently, biologic and genetic research proposed several approaches to inhibit or reduce PCSK9 to improve lipid profile and cardiovascular performance in patients with dyslipidemia, particularly hypercholesterolemia. Of note, PCSK9 is a secreted protein under tight control by multiple modulators. Therefore, elucidating the factors that influence PCSK9 would enhance our understanding of PCSK9 and potentially day-to-day management of these patients at high cardiovascular risk. This review will focus on genetic variants, physiologic processes, pharmacologic agents and pathologic conditions related to PCSK9 in order to assess current and future therapeutic strategies targeting this molecule.
authors.affiliation: Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beilishi Road 167, Beijing 100037, PR China.
authors.forename: Chuan-Jue
authors.initials: CJ
authors.lastname: Cui
authors.affiliation: Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beilishi Road 167, Beijing 100037, PR China.
authors.forename: Sha
authors.initials: S
authors.lastname: Li
authors.affiliation: Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beilishi Road 167, Beijing 100037, PR China. Electronic address: 13901010368@163.com.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Li
mesh_terms: D000367:Age Factors; D050197:Atherosclerosis / Q000378:metabolism; D001384:Azetidines / Q000494:pharmacology; D002784:Cholesterol / Q000378:metabolism*; D002940:Circadian Rhythm; D004032:Diet; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D015444:Exercise; D000069438:Ezetimibe; D058607:Fibric Acids / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D007333:Insulin Resistance; D007674:Kidney Diseases / Q000378:metabolism; D008115:Liver Regeneration; D058990:Molecular Targeted Therapy / Q000379:methods*; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001384:Azetidines; D004365:Drugs, Chinese Herbal; D058607:Fibric Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D000069438:Ezetimibe
keywords: Dyslipidemia; Low-density lipoprotein cholesterol; Proprotein convertase subtilisin/kexin type 9; Review