Proprotein convertase subtilisin/kexin type 9 (PCSK9): From structure–function relation to therapeutic inhibition

Nutrition, Metabolism and Cardiovascular Diseases - Tập 21 Số 11 - Trang 835-843 - 2011
G. Tibolla1,2, Giuseppe Danilo Norata3,1, Roberto Artali4, Fiorella Meneghetti4, Alberico L. Catapano1,2
1Department of Pharmacological Sciences, Università degli Studi di Milano, Italy
2IRCCS MultiMedica, Milan, Italy
3Center for the Study of Atherosclerosis, Società Italiana Studio Aterosclerosi, Ospedale Bassini, Cinisello Balsamo, Italy
4Department of Pharmaceutical Sciences "P. Pratesi", Università degli Studi di Milano, Italy

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2002, Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III) final report, Circulation, 106, 3143, 10.1161/circ.106.25.3143

Ridker, 2008, Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein, N Engl J Med, 359, 2195, 10.1056/NEJMoa0807646

Rao, 1982, The Cincinnati lipid research clinic family study: cultural and biological determinants of lipids and lipoprotein concentrations, Am J Hum Genet, 34, 888

Abifadel, 2003, Mutations in PCSK9 cause autosomal dominant hypercholesterolemia, Nat Genet, 34, 154, 10.1038/ng1161

Benjannet, 2004, NARC-1/PCSK9 and its natural mutants: zymogen cleavage and effects on the low density lipoprotein (LDL) receptor and LDL cholesterol, J Biol Chem, 279, 48865, 10.1074/jbc.M409699200

Cunningham, 2007, Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia, Nat Struct Mol Biol, 14, 413, 10.1038/nsmb1235

Park, 2004, Post-transcriptional regulation of low density lipoprotein receptor protein by proprotein convertase subtilisin/kexin type 9a in mouse liver, J Biol Chem, 279, 50630, 10.1074/jbc.M410077200

Horton, 2003, Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes, Proc Natl Acad Sci U S A, 100, 12027, 10.1073/pnas.1534923100

Maxwell, 2003, Novel putative SREBP and LXR target genes identified by microarray analysis in liver of cholesterol-fed mice, J Lipid Res, 44, 2109, 10.1194/jlr.M300203-JLR200

Jeong, 2008, Sterol-dependent regulation of proprotein convertase subtilisin/kexin type 9 expression by sterol-regulatory element binding protein-2, J Lipid Res, 49, 399, 10.1194/jlr.M700443-JLR200

Dubuc, 2004, Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia, Arterioscler Thromb Vasc Biol, 24, 1454, 10.1161/01.ATV.0000134621.14315.43

Browning, 2010, Fasting reduces plasma proprotein convertase, subtilisin/kexin type 9 and cholesterol biosynthesis in humans, J Lipid Res, 51, 3359, 10.1194/jlr.P009860

Persson, 2010, Circulating proprotein convertase subtilisin kexin type 9 has a diurnal rhythm synchronous with cholesterol synthesis and is reduced by fasting in humans, Arterioscler Thromb Vasc Biol, 30, 2666, 10.1161/ATVBAHA.110.214130

Persson, 2009, Importance of proprotein convertase subtilisin/kexin type 9 in the hormonal and dietary regulation of rat liver low-density lipoprotein receptors, Endocrinology, 150, 1140, 10.1210/en.2008-1281

Langhi, 2008, Activation of the farnesoid X receptor represses PCSK9 expression in human hepatocytes, FEBS Lett, 582, 949, 10.1016/j.febslet.2008.02.038

Cameron, 2008, Berberine decreases PCSK9 expression in HepG2 cells, Atherosclerosis, 201, 266, 10.1016/j.atherosclerosis.2008.02.004

Feingold, 2008, Inflammation stimulates the expression of PCSK9, Biochem Biophys Res Commun, 374, 341, 10.1016/j.bbrc.2008.07.023

Seidah, 2003, The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation, Proc Natl Acad Sci U S A, 100, 928, 10.1073/pnas.0335507100

Essalmani, 2011, In vivo evidence that furin from hepatocytes inactivates PCSK9, J Biol Chem, 286, 4257, 10.1074/jbc.M110.192104

Qian, 2007, Secreted PCSK9 downregulates low density lipoprotein receptor through receptor-mediated endocytosis, J Lipid Res, 48, 1488, 10.1194/jlr.M700071-JLR200

Nassoury, 2007, The cellular trafficking of the secretory proprotein convertase PCSK9 and its dependence on the LDLR, Traffic, 8, 718, 10.1111/j.1600-0854.2007.00562.x

Zhang, 2007, Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation, J Biol Chem, 282, 18602, 10.1074/jbc.M702027200

Yamamoto, 2011, A two step binding model of PCSK9 interaction with the low density lipoprotein receptor, J Biol Chem, 286, 5464, 10.1074/jbc.M110.199042

Maxwell, 2005, Overexpression of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment, Proc Natl Acad Sci U S A, 102, 2069, 10.1073/pnas.0409736102

Poirier, 2008, The proprotein convertase PCSK9 induces the degradation of low density lipoprotein receptor (LDLR) and its closest family members VLDLR and ApoER2, J Biol Chem, 283, 2363, 10.1074/jbc.M708098200

Liu, 2010, PCSK9 is not involved in the degradation of LDL receptors and BACE1 in the adult mouse brain, J Lipid Res, 51, 2611, 10.1194/jlr.M006635

Luo, 2009, Function and distribution of circulating human PCSK9 expressed extrahepatically in transgenic mice, J Lipid Res, 50, 1581, 10.1194/jlr.M800542-JLR200

Mayer, 2008, Annexin A2 is a C-terminal PCSK9-binding protein that regulates endogenous low density lipoprotein receptor levels, J Biol Chem, 283, 31791, 10.1074/jbc.M805971200

Blesa, 2008, A new PCSK9 gene promoter variant affects gene expression and causes autosomal dominant hypercholesterolemia, J Clin Endocrinol Metab, 93, 3577, 10.1210/jc.2008-0269

Shioji, 2004, Genetic variants in PCSK9 affect the cholesterol level in Japanese, J Hum Genet, 49, 109, 10.1007/s10038-003-0114-3

Miyake, 2008, Genetic variants in PCSK9 in the Japanese population: rare genetic variants in PCSK9 might collectively contribute to plasma LDL cholesterol levels in the general population, Atherosclerosis, 196, 29, 10.1016/j.atherosclerosis.2006.12.035

Fasano, 2007, A novel loss of function mutation of PCSK9 gene in white subjects with low-plasma low-density lipoprotein cholesterol, Arterioscler Thromb Vasc Biol, 27, 677, 10.1161/01.ATV.0000255311.26383.2f

Zhao, 2006, Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote, Am J Hum Genet, 79, 514, 10.1086/507488

Berge, 2006, Missense mutations in the PCSK9 gene are associated with hypocholesterolemia and possibly increased response to statin therapy, Arterioscler Thromb Vasc Biol, 26, 1094, 10.1161/01.ATV.0000204337.81286.1c

Fasano, 2009, Degradation of LDLR protein mediated by ‘gain of function’ PCSK9 mutants in normal and ARH cells, Atherosclerosis, 203, 166, 10.1016/j.atherosclerosis.2008.10.027

Homer, 2008, Identification and characterization of two non-secreted PCSK9 mutants associated with familial hypercholesterolemia in cohorts from New Zealand and South Africa, Atherosclerosis, 196, 659, 10.1016/j.atherosclerosis.2007.07.022

Cohen, 2005, Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9, Nat Genet, 37, 161, 10.1038/ng1509

Cameron, 2008, Characterization of novel mutations in the catalytic domain of the PCSK9 gene, J Intern Med, 263, 420, 10.1111/j.1365-2796.2007.01915.x

Allard, 2005, Novel mutations of the PCSK9 gene cause variable phenotype of autosomal dominant hypercholesterolemia, Hum Mutat, 26, 497, 10.1002/humu.9383

Kotowski, 2006, A spectrum of PCSK9 alleles contributes to plasma levels of low-density lipoprotein cholesterol, Am J Hum Genet, 78, 410, 10.1086/500615

Bourbon, 2008, Familial hypercholesterolaemia in Portugal, Atherosclerosis, 196, 633, 10.1016/j.atherosclerosis.2007.07.019

Dubuc, 2010, A new method for measurement of total plasma PCSK9: clinical applications, J Lipid Res, 51, 140, 10.1194/jlr.M900273-JLR200

Cameron, 2009, Mutation S462P in the PCSK9 gene reduces secretion of mutant PCSK9 without affecting the autocatalytic cleavage, Atherosclerosis, 203, 161, 10.1016/j.atherosclerosis.2008.10.007

Pisciotta, 2006, Additive effect of mutations in LDLR and PCSK9 genes on the phenotype of familial hypercholesterolemia, Atherosclerosis, 186, 433, 10.1016/j.atherosclerosis.2005.08.015

Timms, 2004, A mutation in PCSK9 causing autosomal-dominant hypercholesterolemia in a Utah pedigree, Hum Genet, 114, 349, 10.1007/s00439-003-1071-9

Leren, 2004, Mutations in the PCSK9 gene in Norwegian subjects with autosomal dominant hypercholesterolemia, Clin Genet, 65, 419, 10.1111/j.0009-9163.2004.0238.x

Naoumova, 2005, Severe hypercholesterolemia in four British families with the D374Y mutation in the PCSK9 gene: long-term follow-up and treatment response, Arterioscler Thromb Vasc Biol, 25, 2654, 10.1161/01.ATV.0000190668.94752.ab

Norata, 2010, Effects of PCSK9 variants on common carotid artery intima media thickness and relation to ApoE alleles, Atherosclerosis, 208, 177, 10.1016/j.atherosclerosis.2009.06.023

Hooper, 2007, The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population, Atherosclerosis, 193, 445, 10.1016/j.atherosclerosis.2006.08.039

Cameron, 2006, Effect of mutations in the PCSK9 gene on the cell surface LDL receptors, Hum Mol Genet, 15, 1551, 10.1093/hmg/ddl077

Cariou, 2009, PCSK9 dominant negative mutant results in increased LDL catabolic rate and familial hypobetalipoproteinemia, Arterioscler Thromb Vasc Biol, 29, 2191, 10.1161/ATVBAHA.109.194191

Lagace, 2006, Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice, J Clin Invest, 116, 2995, 10.1172/JCI29383

Lakoski, 2009, Genetic and metabolic determinants of plasma PCSK9 levels, J Clin Endocrinol Metab, 94, 2537, 10.1210/jc.2009-0141

Baass, 2009, Plasma PCSK9 is associated with age, sex, and multiple metabolic markers in a population-based sample of children and adolescents, Clin Chem, 55, 1637, 10.1373/clinchem.2009.126987

Cui, 2010, Serum PCSK9 is associated with multiple metabolic factors in a large Han Chinese population, Atherosclerosis, 213, 632, 10.1016/j.atherosclerosis.2010.09.027

Alborn, 2007, Serum proprotein convertase subtilisin kexin type 9 is correlated directly with serum LDL cholesterol, Clin Chem, 53, 1814, 10.1373/clinchem.2007.091280

Welder, 2010, High-dose atorvastatin causes a rapid sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol, J Lipid Res, 51, 2714, 10.1194/jlr.M008144

Ouguerram, 2004, Apolipoprotein B100 metabolism in autosomal-dominant hypercholesterolemia related to mutations in PCSK9, Arterioscler Thromb Vasc Biol, 24, 1448, 10.1161/01.ATV.0000133684.77013.88

Lambert, 2006, Fasting induces hyperlipidemia in mice overexpressing proprotein convertase subtilisin kexin type 9: lack of modulation of very-low-density lipoprotein hepatic output by the low-density lipoprotein receptor, Endocrinology, 147, 4985, 10.1210/en.2006-0098

Lalanne, 2005, Wild-type PCSK9 inhibits LDL clearance but does not affect apoB-containing lipoprotein production in mouse and cultured cells, J Lipid Res, 46, 1312, 10.1194/jlr.M400396-JLR200

Chan, 2009, Plasma proprotein convertase subtilisin/kexin type 9: a marker of LDL apolipoprotein B-100 catabolism?, Clin Chem, 55, 2049, 10.1373/clinchem.2009.128645

Careskey, 2008, Atorvastatin increases human serum levels of proprotein convertase subtilisin/kexin type 9, J Lipid Res, 49, 394, 10.1194/jlr.M700437-JLR200

Troutt, 2010, Fenofibrate treatment increases human serum proprotein convertase subtilisin kexin type 9 levels, J Lipid Res, 51, 345, 10.1194/jlr.M000620

Lambert, 2008, Plasma PCSK9 concentrations correlate with LDL and total cholesterol in diabetic patients and are decreased by fenofibrate treatment, Clin Chem, 54, 1038, 10.1373/clinchem.2007.099747

Nilsson, 2007, Bile acids and lipoprotein metabolism: effects of cholestyramine and chenodeoxycholic acid on human hepatic mRNA expression, Biochem Biophys Res Commun, 357, 707, 10.1016/j.bbrc.2007.03.196

Rashid, 2005, Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9, Proc Natl Acad Sci U S A, 102, 5374, 10.1073/pnas.0501652102

Cohen, 2006, Sequence variations in PCSK9, low LDL, and protection against coronary heart disease, N Engl J Med, 354, 1264, 10.1056/NEJMoa054013

Chan, 2009, A proprotein convertase subtilisin/kexin type 9 neutralizing antibody reduces serum cholesterol in mice and nonhuman primates, Proc Natl Acad Sci U S A, 106, 9820, 10.1073/pnas.0903849106

Graham, 2007, Antisense inhibition of proprotein convertase subtilisin/kexin type 9 reduces serum LDL in hyperlipidemic mice, J Lipid Res, 48, 763, 10.1194/jlr.C600025-JLR200

Frank-Kamenetsky, 2008, Therapeutic RNAi targeting PCSK9 acutely lowers plasma cholesterol in rodents and LDL cholesterol in nonhuman primates, Proc Natl Acad Sci U S A, 105, 11915, 10.1073/pnas.0805434105

Gupta, 2010, A locked nucleic acid antisense oligonucleotide (LNA) silences PCSK9 and enhances LDLR expression in vitro and in vivo, PLoS One, 5, e10682, 10.1371/journal.pone.0010682

Ni, 2011, A proprotein convertase subtilisin-like/kexin type 9 (PCSK9)-binding antibody that structurally mimics the EGF(A) domain of LDL-receptor reduces free circulating PCSK9 and LDL-cholesterol, J Lipid Res, 52, 78, 10.1194/jlr.M011445

Ni, 2011, A PCSK9-binding antibody that structurally mimics the EGF(A) domain of LDL-receptor reduces LDL cholesterol in vivo, J Lipid Res, 52, 78, 10.1194/jlr.M011445

Seidah, 2007, The proprotein convertases are potential targets in the treatment of dyslipidemia, J Mol Med, 85, 685, 10.1007/s00109-007-0172-7

Grefhorst, 2008, Plasma PCSK9 preferentially reduces liver LDL receptors in mice, J Lipid Res, 49, 1303, 10.1194/jlr.M800027-JLR200

Hedrick, 2009, Targeting PCSK9 for the treatment of hypercholesterolemia, Curr Opin Investig Drugs, 10, 938