The role of PCSK9 in intestinal lipoprotein metabolism: synergism of statin and ezetimibe.
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.
['Fazio|Sergio|S|']
D000818:Animals D001384:Azetidines D002784:Cholesterol D004338:Drug Combinations D004357:Drug Synergism D050171:Dyslipidemias D000069499:Ezetimibe, Simvastatin Drug Combination D006801:Humans D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors D007408:Intestinal Absorption D007422:Intestines D008074:Lipoproteins D000071449:Proprotein Convertase 9 D043484:Proprotein Convertases D011973:Receptors, LDL D012697:Serine Endopeptidases D019821:Simvastatin D016896:Treatment Outcome
PCSK9 Ezetimibe LDL receptor