Review on PCSK9: A Pertinent Therapeutic Target in Cardiovascular Disease

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Cohen, J.; Pertsemlidis, A.; Kotowski, I.K.; Graham, R.; Garcia, C.K.; Hobbs, H.H. Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9. Nat. Genet., 2005, 37(2), 161-165.
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Cohen, J.C.; Boerwinkle, E.; Mosley, T.H., Jr; Hobbs, H.H. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N. Engl. J. Med., 2006, 354(12), 1264-1272.
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Hooper, A.J.; Marais, A.D.; Tanyanyiwa, D.M.; Burnett, J.R. The C679X mutation in PCSK9 is present and lowers blood cholesterol in a Southern African population. Atherosclerosis, 2007, 193(2), 445-448.
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Fasano, T.; Cefalù, A.B.; Di Leo, E.; Noto, D.; Pollaccia, D.; Bocchi, L.; Valenti, V.; Bonardi, R.; Guardamagna, O.; Averna, M.; Tarugi, P. A novel loss of function mutation of PCSK9 gene in white subjects with low-plasma low-density lipoprotein cholesterol. Arterioscler. Thromb. Vasc. Biol., 2007, 27(3), 677-681.
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Zhao, Z.; Tuakli-Wosornu, Y.; Lagace, T.A.; Kinch, L.; Grishin, N.V.; Horton, J.D.; Cohen, J.C.; Hobbs, H.H. Molecular characterization of loss-of-function mutations in PCSK9 and identification of a compound heterozygote. Am. J. Hum. Genet., 2006, 79(3), 514-523.
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Sabatine, M.S.; Giugliano, R.P.; Keech, A.C.; Honarpour, N.; Wiviott, S.D.; Murphy, S.A.; Kuder, J.F.; Wang, H.; Liu, T.; Wasserman, S.M.; Sever, P.S.; Pedersen, T.R. Evolocumab and clinical outcomes in patients with cardiovascular disease. N. Engl. J. Med., 2017, 376(18), 1713-1722.
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Cunningham, D.; Danley, D.E.; Geoghegan, K.F.; Griffor, M.C.; Hawkins, J.L.; Subashi, T.A.; Varghese, A.H.; Ammirati, M.J.; Culp, J.S.; Hoth, L.R.; Mansour, M.N.; McGrath, K.M.; Seddon, A.P.; Shenolikar, S.; Stutzman-Engwall, K.J.; Warren, L.C.; Xia, D.; Qiu, X. Structural and biophysical studies of PCSK9 and its mutants linked to familial hypercholesterolemia. Nat. Struct. Mol. Biol., 2007, 14(5), 413-419.
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Hampton, E.N.; Knuth, M.W.; Li, J.; Harris, J.L.; Lesley, S.A.; Spraggon, G. The self-inhibited structure of full-length PCSK9 at 1.9 Å reveals structural homology with resistin within the Cterminal domain. Proc. Natl. Acad. Sci., 2007, 104(37), 14604-14609.
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Piper, D.E.; Jackson, S.; Liu, Q.; Romanow, W.G.; Shetterly, S.; Thibault, S.T.; Shan, B.; Walker, N.P.C. The crystal structure of PCSK9: A regulator of plasma LDL-cholesterol. Structure, 2007, 15(5), 545-552.
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Kwon, H.J.; Lagace, T.A.; McNutt, M.C.; Horton, J.D.; Deisenhofer, J. Molecular basis for LDL receptor recognition by PCSK9. Proc. Natl. Acad. Sci., 2008, 105(6), 1820-1825.
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Fisher, T.S.; Surdo, P.L.; Pandit, S.; Mattu, M.; Santoro, J.C.; Wisniewski, D.; Cummings, R.T.; Calzetta, A.; Cubbon, R.M.; Fischer, P.A.; Tarachandani, A.; De Francesco, R.; Wright, S.D.; Sparrow, C.P.; Carfi, A.; Sitlani, A. Effects of pH and low density lipoprotein (LDL) on PCSK9-dependent LDL receptor regulation. J. Biol. Chem., 2007, 282(28), 20502-20512.
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Pearlstein, R.A.; Hu, Q.Y.; Zhou, J.; Yowe, D.; Levell, J.; Dale, B.; Kaushik, V.K.; Daniels, D.; Hanrahan, S.; Sherman, W.; Abel, R. New hypotheses about the structure-function of proprotein convertase subtilisin/kexin type 9: Analysis of the epidermal growth factor- like repeat A docking site using WaterMap. Proteins, 2010, 78(12), n/a.
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Zhang, D.W.; Garuti, R.; Tang, W.J.; Cohen, J.C.; Hobbs, H.H. Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor. Proc. Natl. Acad. Sci., 2008, 105(35), 13045-13050.
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Mousavi, S.A.; Berge, K.E.; Berg, T.; Leren, T.P. Affinity and kinetics of proprotein convertase subtilisin/kexin type 9 binding to low-density lipoprotein receptors on HepG2 cells. FEBS J., 2011, 278(16), 2938-2950.
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Ai, X.; Fischer, P.; Palyha, O.C.; Wisniewski, D.; Hubbard, B.; Akinsanya, K.; Strack, A.M.; Ehrhardt, A.G. Utilizing HaloTag technology to track the fate of PCSK9 from intracellular vs. extracellular sources. Curr. Chem. Genomics, 2012, 6, 38-47.
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Qian, Y.W.; Schmidt, R.J.; Zhang, Y.; Chu, S.; Lin, A.; Wang, H.; Wang, X.; Beyer, T.P.; Bensch, W.R.; Li, W.; Ehsani, M.E.; Lu, D.; Konrad, R.J.; Eacho, P.I.; Moller, D.E.; Karathanasis, S.K.; Cao, G. Secreted PCSK9 downregulates low density lipoprotein receptor through receptor-mediated endocytosis. J. Lipid Res., 2007, 48(7), 1488-1498.
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Seidah, N.G.; Benjannet, S.; Wickham, L.; Marcinkiewicz, J.; Jasmin, S.B.; Stifani, S.; Basak, A.; Prat, A.; Chrétien, M. The secretory pro-protein convertase neural apoptosis-regulated convertase 1 (NARC-1): Liver regeneration and neuronal differentiation. Proc. Natl. Acad. Sci., 2003, 100(3), 928-933.
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Cameron, J.; Holla, Ø.L.; Ranheim, T.; Kulseth, M.A.; Berge, K.E.; Leren, T.P. Effect of mutations in the PCSK9 gene on the cell surface LDL receptors. Hum. Mol. Genet., 2006, 15(9), 1551-1558.
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Dubuc, G.; Chamberland, A.; Wassef, H.; Davignon, J.; Seidah, N.G.; Bernier, L.; Prat, A. Statins upregulate PCSK9, the gene encoding the proprotein convertase neural apoptosis-regulated convertase-1 implicated in familial hypercholesterolemia. Arterioscler. Thromb. Vasc. Biol., 2004, 24(8), 1454-1459.
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Glerup, S.; Schulz, R.; Laufs, U.; Schlüter, K.D. Physiological and therapeutic regulation of PCSK9 activity in cardiovascular disease. Basic Res. Cardiol., 2017, 112(3), 32.
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