title: The role of PCSK9 in intestinal lipoprotein metabolism: synergism of statin and ezetimibe.
abstract: Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a major role in the regulation of lipoprotein metabolism, mostly through control of low-density lipoprotein receptor degradation. Depletion of cellular cholesterol causes a compensatory increase in plasma PCSK9 levels, which can diminish the cholesterol-lowering power of statins and may lead to the overproduction of intestinal lipoproteins, mainly thorough the up regulation of microsomal triglyceride transfer protein and the Niemann-Pick C1-like 1 protein, the target of ezetimibe. Thus, ezetimibe therapy may counter this unwanted effect of statins, providing an additional theoretical rationale for combining the effect of ezetimibe on intestinal cholesterol absorption and that of statins on cholesterol synthesis.
authors: Cornelius Vanderbilt Professor of Medicine Professor of Pathology, Immunology, and Microbiology Chief, Section of CVD Prevention Vanderbilt University School of Medicine, Nashville, Tennessee, USA. Electronic address: fazio@ohsu.edu.
authors: Sergio
authors: S
authors: Fazio
mesh_terms: D000818:Animals; D001384:Azetidines / Q000009:adverse effects / Q000627:therapeutic use*; D002784:Cholesterol / Q000097:blood; D004338:Drug Combinations; D004357:Drug Synergism; D050171:Dyslipidemias / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology; D000069499:Ezetimibe, Simvastatin Drug Combination; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D007408:Intestinal Absorption / Q000187:drug effects; D007422:Intestines / Q000187:drug effects* / Q000201:enzymology; D008074:Lipoproteins / Q000097:blood*; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000378:metabolism*; D011973:Receptors, LDL / Q000187:drug effects / Q000378:metabolism; D012697:Serine Endopeptidases / Q000378:metabolism*; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001384:Azetidines; D004338:Drug Combinations; D000069499:Ezetimibe, Simvastatin Drug Combination; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C573412:LDLR protein, human; D008074:Lipoproteins; D011973:Receptors, LDL; D002784:Cholesterol; D019821:Simvastatin; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases
keywords: Ezetimibe; LDL receptor; PCSK9