Cited by 30Lipoproteins and Cardiovascular HealthCholesterol and Lipid MetabolismLipid metabolism and disorders

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PCSK9 inhibition to reduce cardiovascular disease risk: recent findings from the biology of PCSK9

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Tavori, Hagai, Giunzioni, Ilaria, Fazio, Sergio·2015·Current Opinion in Endocrinology, Diabetes & Obesity

DOI 10.1097/med.0000000000000137PMC PMC4384821

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Abstract

PURPOSE OF REVIEW: Review novel insights into the biology of proprotein convertase subtilisin/kexin 9 (PCSK9) that may explain the extreme efficiency of PCSK9 inhibition and the unexpected metabolic effects resulting from PCSK9 monoclonal antibody therapy, and may identify additional patients as target of therapy. RECENT FINDINGS: For over 20 years, the practical knowledge of cholesterol metabolism has centered around cellular mechanisms, and around the idea that statin therapy is the essential step to control metabolic abnormalities for cardiovascular risk management. This view has been embraced by the recent AHA/ACC guidelines, but is being challenged by recent studies including nonstatin medications and by the development of a new class of cholesterol-lowering agents that seems destined to early US Food and Drug Administration approval. The discovery of PCSK9 - a circulating protein that regulates hepatic low-density lipoprotein (LDL) receptor and serum LDL cholesterol levels - has led to a race for its therapeutic inhibition. Recent findings on PCSK9 regulation and pleiotropic effects will help identify additional patient groups likely to benefit from the inhibitory therapy and unravel the full potential of PCSK9 inhibition therapy. SUMMARY: Injectable human monoclonal antibodies to block the interaction between PCSK9 and LDL receptor are demonstrating extraordinary efficacy (LDL reductions of up to 70%) and almost the absence of any side-effects. A more moderate effect is seen on other lipoprotein parameters, with the exception of lipoprotein(a) levels. We describe mechanisms that can explain the effect on lipoprotein(a), predict a potential effect on postprandial triglyderides, and suggest a new category of patients for anti-PCSK9 therapy.

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2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines
Stone, N. J., Robinson, J. G., Lichtenstein, A. H., Bairey Merz, C. N., Blum, C. B., Eckel, R. H., Goldberg, A. C., Gordon, D., Levy, D., Lloyd-Jones, D. M., et al. (2014) · Circulation · doi:10.1161/01.cir.0000437738.63853.7a · Cited by 7,081
The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor
Brown, M. S., & Goldstein, J. L. (1997) · Cell · doi:10.1016/s0092-8674(00)80213-5 · Cited by 3,834
Genetic Variants Associated with Lp(a) Lipoprotein Level and Coronary Disease
Clarke, R., Peden, J. F., Hopewell, J. C., Kyriakou, T., Goel, A., Heath, S. C., Parish, S., Barlera, S., Franzosi, M. G., Rust, S., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0902604 · Cited by 1,671
Low LDL cholesterol in individuals of African descent resulting from frequent nonsense mutations in PCSK9
Cohen, J., Pertsemlidis, A., Kotowski, I. K., Graham, R., Garcia, C. K., & Hobbs, H. H. (2005) · Nature Genetics · doi:10.1038/ng1509 · Cited by 1,381
Loss-of-Function Mutations in APOC3, Triglycerides, and Coronary Disease
The TG and HDL Working Group of the Exome Sequencing Project, N. H. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1307095 · Cited by 1,071
Lipoprotein(a) and Coronary Heart Disease
Danesh, J., Collins, R., & Peto, R. (2000) · Circulation · doi:10.1161/01.cir.102.10.1082 · Cited by 938
Loss-of-Function Mutations in APOC3 and Risk of Ischemic Vascular Disease
Jørgensen, A. B., Frikke-Schmidt, R., Nordestgaard, B. G., & Tybjærg-Hansen, A. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1308027 · Cited by 919
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
Zhang, D.-W., Lagace, T. A., Garuti, R., Zhao, Z., McDonald, M., Horton, J. D., Cohen, J. C., & Hobbs, H. H. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702027200 · Cited by 788
PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial
Raal, F. J., Stein, E. A., Dufour, R., Turner, T., Civeira, F., Burgess, L., Langslet, G., Scott, R., Olsson, A. G., Sullivan, D., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(14)61399-4 · Cited by 756
Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial
Raal, F. J., Honarpour, N., Blom, D. J., Hovingh, G. K., Xu, F., Scott, R. C., Wasserman, S. M., & Stein, E. A. (2014) · The Lancet · doi:10.1016/s0140-6736(14)61374-x · Cited by 746
Cholesterol Lowering With Statin Drugs, Risk of Stroke, and Total Mortality: An Overview of Randomized Trials
Hebert, P. R. (1997) · JAMA · doi:10.1001/jama.1997.03550040069040 · Cited by 740
A 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia
Blom, D. J., Hala, T., Bolognese, M., Lillestol, M. J., Toth, P. D., Burgess, L., Ceska, R., Roth, E., Koren, M. J., Ballantyne, C. M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1316222 · Cited by 720
Decreased plasma cholesterol and hypersensitivity to statins in mice lacking Pcsk9
Rashid, S., Curtis, D. E., Garuti, R., Anderson, N. N., Bashmakov, Y., Ho, Y. K., Hammer, R. E., Moon, Y.-A., & Horton, J. D. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501652102 · Cited by 679
Effect of a Monoclonal Antibody to PCSK9 on LDL Cholesterol
Stein, E. A., Mellis, S., Yancopoulos, G. D., Stahl, N., Logan, D., Smith, W. B., Lisbon, E., Gutierrez, M., Webb, C., Wu, R., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1105803 · Cited by 664
National Cholesterol Education Program Versus World Health Organization Metabolic Syndrome in Relation to All-Cause and Cardiovascular Mortality in the San Antonio Heart Study
Hunt, K. J., Resendez, R. G., Williams, K., Haffner, S. M., & Stern, M. P. (2004) · Circulation · doi:10.1161/01.cir.0000140762.04598.f9 · Cited by 662
Molecular Characterization of Loss-of-Function Mutations in PCSK9 and Identification of a Compound Heterozygote
Zhao, Z., Tuakli-Wosornu, Y., Lagace, T. A., Kinch, L. N., Grishin, N. V., Horton, J. D., Cohen, J. C., & Hobbs, H. H. (2006) · The American Journal of Human Genetics · doi:10.1086/507488 · Cited by 642
NARC-1/PCSK9 and Its Natural Mutants
Benjannet, S., Rhainds, D., Essalmani, R., Mayne, J., Wickham, L., Jin, W., Asselin, M.-C., Hamelin, J., Varret, M., Allard, D., et al. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m409699200 · Cited by 587
Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial
Fitzgerald, K. J., Frank-Kamenetsky, M. D., Shulga‐Morskaya, S., Liebow, A., Bettencourt, B. R., Sutherland, J. E., Hutabarat, R. M., Clausen, V. A., Karsten, V., Cehelsky, J. E., et al. (2013) · The Lancet · doi:10.1016/s0140-6736(13)61914-5 · Cited by 586
Cholesterol Lowering With Statin Drugs, Risk of Stroke, and Total Mortality
Hebert, P. R., Gaziano, J. M., Chan, K. S., & Hennekens, C. H. (1998) · Survey of Anesthesiology · doi:10.1097/00132586-199806000-00060 · Cited by 506
Low-Density Lipoprotein Cholesterol–Lowering Effects of AMG 145, a Monoclonal Antibody to Proprotein Convertase Subtilisin/Kexin Type 9 Serine Protease in Patients With Heterozygous Familial Hypercholesterolemia
Raal, F. J., Scott, R. C., Somaratne, R. M., Bridges, I. M., Li, G., Wasserman, S. M., & Stein, E. A. (2012) · Circulation · doi:10.1161/circulationaha.112.144055 · Cited by 506
Effect of Evolocumab or Ezetimibe Added to Moderate- or High-Intensity Statin Therapy on LDL-C Lowering in Patients With Hypercholesterolemia: The LAPLACE-2 Randomized Clinical Trial
Robinson, J. G., Nedergaard, B. S., Rogers, W. J., Fialkow, J., Neutel, J. M., Ramstad, D., Somaratne, R., Legg, J. C., Nelson, P., Scott, R., et al. (2014) · JAMA · doi:10.1001/jama.2014.4030 · Cited by 496
The Proprotein Convertase PCSK9 Induces the Degradation of Low Density Lipoprotein Receptor (LDLR) and Its Closest Family Members VLDLR and ApoER2
Poirier, S., Mayer, G., Benjannet, S., Bergeron, E., Marcinkiewicz, J., Nassoury, N., Mayer, H., Nimpf, J., Prat, A., & Seidah, N. G. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708098200 · Cited by 477
Atorvastatin with or without an Antibody to PCSK9 in Primary Hypercholesterolemia
Roth, E. M., McKenney, J. M., Hanotin, C., Asset, G., & Stein, E. A. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1201832 · Cited by 462
Human plasma lipoprotein [a]. Structural properties.
Gaubatz, J. W., Heideman, C. L., Gotto, A. M., et al. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)32663-2 · Cited by 454
Post-transcriptional Regulation of Low Density Lipoprotein Receptor Protein by Proprotein Convertase Subtilisin/Kexin Type 9a in Mouse Liver
Park, S. W., Moon, Y.-A., & Horton, J. D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m410077200 · Cited by 452
Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study
Giugliano, R. P., Desai, N. R., Kohli, P., Rogers, W. J., Somaratne, R. M., Huang, F., Liu, T., Mohanavelu, S., Hoffman, E. B., McDonald, S. T., et al. (2012) · The Lancet · doi:10.1016/s0140-6736(12)61770-x · Cited by 429
Anti-PCSK9 Monotherapy for Hypercholesterolemia
Koren, M. J., Lundqvist, P., Bolognese, M., Neutel, J. M., Monsalvo, M. L., Yang, J., Kim, J. B., Scott, R., Wasserman, S. M., & Bays, H. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.03.018 · Cited by 411
Reduction in Lipoprotein(a) With PCSK9 Monoclonal Antibody Evolocumab (AMG 145)
Raal, F. J., Giugliano, R. P., Sabatine, M. S., Koren, M. J., Langslet, G., Bays, H. E., Blom, D. J., Eriksson, M., Dent, R. E., Wasserman, S. M., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.01.006 · Cited by 365
Sterol-dependent regulation of proprotein convertase subtilisin/kexin type 9 expression by sterol-regulatory element binding protein-2
Jeong, H. J., Lee, H.-S., Kim, K.-S., Kim, Y.-K., Yoon, D., & Park, S. W. (2008) · Journal of Lipid Research · doi:10.1194/jlr.m700443-jlr200 · Cited by 331
Atorvastatin increases human serum levels of proprotein convertase subtilisin/kexin type 9
Careskey, H. E., Davis, R., Alborn, W. E., Troutt, J. S., Cao, G., & Konrad, R. J. (2007) · Journal of Lipid Research · doi:10.1194/jlr.m700437-jlr200 · Cited by 318
Hepatic PCSK9 Expression Is Regulated by Nutritional Status via Insulin and Sterol Regulatory Element-binding Protein 1c
Costet, P., Cariou, B., Lambert, G. C., Lalanne, F., Lardeux, B. R., Jarnoux, A. L., Grefhorst, A., Staels, B., & Krempf, M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m508582200 · Cited by 315
Assessment and clinical relevance of non-fasting and postprandial triglycerides: an expert panel statement
D. Kolovou, G., P. Mikhailidis, D., Kovar, J., Lairon, D., G. Nordestgaard, B., Chye Ooi, T., Perez-Martinez, P., Bilianou, H., Anagnostopoulou, K., & Panotopoulos, G. (2011) · Current Vascular Pharmacology · doi:10.2174/157016111795495549 · Cited by 306
Effect of the Proprotein Convertase Subtilisin/Kexin 9 Monoclonal Antibody, AMG 145, in Homozygous Familial Hypercholesterolemia
Stein, E. A., Honarpour, N., Wasserman, S. M., Xu, F., Scott, R., & Raal, F. J. (2013) · Circulation · doi:10.1161/circulationaha.113.004678 · Cited by 300
Apolipoprotein B Synthesis Inhibition With Mipomersen in Heterozygous Familial Hypercholesterolemia
Stein, E. A., Dufour, R., Gagné, C., Gaudet, D., East, C. A., Donovan, J. M., Chin, W., Tribble, D. L., & McGowan, M. P. (2012) · Circulation · doi:10.1161/circulationaha.112.104125 · Cited by 297
The Proprotein Convertase (PC) PCSK9 Is Inactivated by Furin and/or PC5/6A
Benjannet, S., Rhainds, D., Hamelin, J., Nassoury, N., & Seidah, N. G. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m606495200 · Cited by 263
Catalytic Activity Is Not Required for Secreted PCSK9 to Reduce Low Density Lipoprotein Receptors in HepG2 Cells
McNutt, M. C., Lagace, T. A., & Horton, J. D. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.c700095200 · Cited by 251
Monotherapy with the PCSK9 inhibitor alirocumab versus ezetimibe in patients with hypercholesterolemia: Results of a 24week, double-blind, randomized Phase 3 trial
Roth, E. M., Taskinen, M., Ginsberg, H. N., Kastelein, J. J. P., Colhoun, H. M., Robinson, J. G., Merlet, L., Pordy, R. C., & Baccara‐Dinet, M. T. (2014) · International Journal of Cardiology · doi:10.1016/j.ijcard.2014.06.049 · Cited by 248
An assessment by the Statin Liver Safety Task Force: 2014 update
Bays, H. E., Cohen, D. E., Chalasani, N., & Harrison, S. A. (2014) · Journal of clinical lipidology · doi:10.1016/j.jacl.2014.02.011 · Cited by 235
A new method for measurement of total plasma PCSK9: clinical applications
Dubuc, G., Tremblay, M., Paré, G., Jacques, H., Hamelin, J., Benjannet, S., Boulet, L., Genest, J. J., Bernier, L., Seidah, N. G., et al. (2009) · Journal of Lipid Research · doi:10.1194/jlr.m900273-jlr200 · Cited by 231
High-dose atorvastatin causes a rapid sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol
Welder, G., Zineh, I., Pacanowski, M. A., Troutt, J. S., Cao, G., & Konrad, R. J. (2010) · Journal of Lipid Research · doi:10.1194/jlr.m008144 · Cited by 227
Plasma PCSK9 levels are significantly modified by statins and fibrates in humans
Mayne, J., Dewpura, T., Raymond, A., Cousins, M., Chaplin, A., Lahey, K. A., LaHaye, S. A., Mbikay, M., Ooi, T. C., & Chrétien, M. (2008) · Lipids in Health and Disease · doi:10.1186/1476-511x-7-22 · Cited by 224
Statin treatment and new-onset diabetes: A review of proposed mechanisms
Brault, M., Ray, J., Sandoval, Y.-H. G., Mantzoros, C. S., & Daskalopoulou, S. S. (2014) · Metabolism · doi:10.1016/j.metabol.2014.02.014 · Cited by 218
Gene Inactivation of Proprotein Convertase Subtilisin/Kexin Type 9 Reduces Atherosclerosis in Mice
Denis, M., Marcinkiewicz, J., Zaid, A., Gauthier, D., Poirier, S., Lazure, C., Seidah, N. G., & Prat, A. (2012) · Circulation · doi:10.1161/circulationaha.111.057406 · Cited by 212
Effect of Alirocumab, a Monoclonal Proprotein Convertase Subtilisin/Kexin 9 Antibody, on Lipoprotein(a) Concentrations (a Pooled Analysis of 150 mg Every Two Weeks Dosing from Phase 2 Trials)
Gaudet, D., Kereiakes, D. J., McKenney, J. M., Roth, E. M., Hanotin, C., Gipe, D. A., Du, Y. E., Ferrand, A.-C., Ginsberg, H. N., & Stein, E. A. (2014) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2014.05.060 · Cited by 211
Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor
Zhang, D.-W., Garuti, R., Tang, W.-J., Cohen, J. C., & Hobbs, H. H. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0806312105 · Cited by 208
The Multifaceted Proprotein Convertases: Their Unique, Redundant, Complementary, and Opposite Functions
Seidah, N. G., Sadr, M. S., Chrétien, M., & Mbikay, M. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.r113.481549 · Cited by 182
Low density lipoprotein binds to proprotein convertase subtilisin/kexin type-9 (PCSK9) in human plasma and inhibits PCSK9-mediated low density lipoprotein receptor degradation
Kosenko, T., Golder, M., Leblond, G., Weng, W., & Lagace, T. A. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.421370 · Cited by 181
AMG145, a Monoclonal Antibody Against Proprotein Convertase Subtilisin Kexin Type 9, Significantly Reduces Lipoprotein(a) in Hypercholesterolemic Patients Receiving Statin Therapy
Desai, N. R., Kohli, P., Giugliano, R. P., O’Donoghue, M. L., Somaratne, R. M., Zhou, J., Hoffman, E. B., Huang, F., Rogers, W. J., Wasserman, S. M., et al. (2013) · Circulation · doi:10.1161/circulationaha.113.001969 · Cited by 179
Serum Proprotein Convertase Subtilisin/Kexin Type 9 and Cell Surface Low-Density Lipoprotein Receptor: Evidence for a Reciprocal Regulation
Tavori, H., Fan, D., Blakemore, J. L., Yancey, P. G., Ding, L., Linton, M. F., & Fazio, S. (2013) · Circulation · doi:10.1161/circulationaha.113.001592 · Cited by 178
Self-citation
Proprotein Convertase Subtilisin Kexin Type 9 Null Mice Are Protected From Postprandial Triglyceridemia
May, C. L., Kourimate, S., Langhi, C., Chétiveaux, M., Jarry, A., Coméra, C., Collet, X., Kuipers, F., Krempf, M., Cariou, B., et al. (2009) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.181586 · Cited by 171
Differential expression of oxidation-specific epitopes and apolipoprotein(a) in progressing and ruptured human coronary and carotid atherosclerotic lesions
van Dijk, R. A., Kolodgie, F. D., Ravandi, A., Leibundgut, G., Hu, P., Prasad, A., Mahmud, E., Dennis, E. A., Curtiss, L. K., Witztum, J. L., et al. (2012) · Journal of Lipid Research · doi:10.1194/jlr.p030890 · Cited by 169
Regulation of hepatic LDL receptors by mTORC1 and PCSK9 in mice
Ai, D., Chen, C., Han, S., Ganda, A., Murphy, A. J., Haeusler, R. A., Thorp, E. B., Accili, D., Horton, J. D., & Tall, A. R. (2012) · Journal of Clinical Investigation · doi:10.1172/jci61919 · Cited by 169
Efficacy and Safety of Rosuvastatin Therapy for Children With Familial Hypercholesterolemia
Avis, H. J., Hutten, B. A., Gagné, C., Langslet, G., McCrindle, B. W., Wiegman, A., Hsia, J. A., Kastelein, J. J. P., & Stein, E. A. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.10.042 · Cited by 168
The proprotein convertases are potential targets in the treatment of dyslipidemia
Seidah, N. G., & Prat, A. (2007) · Journal of Molecular Medicine · doi:10.1007/s00109-007-0172-7 · Cited by 155
Proprotein Convertase Subtilisin Kexin Type 9 Promotes Intestinal Overproduction of Triglyceride-Rich Apolipoprotein B Lipoproteins Through Both Low-Density Lipoprotein Receptor–Dependent and –Independent Mechanisms
Rashid, S., Tavori, H., Brown, P. E., Linton, M. F., He, J., Giunzioni, I., & Fazio, S. (2014) · Circulation · doi:10.1161/circulationaha.113.006720 · Cited by 147
Self-citation
PCSK9 plays a significant role in cholesterol homeostasis and lipid transport in intestinal epithelial cells
Levy, E. H., Ouadda, A. B. D., Spahis, S., Sané, A. T., Garofalo, C., Grenier, É., Emonnot, L., Yara, S., Couture, P., Beaulieu, J., et al. (2013) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2013.01.023 · Cited by 141
Elevated PCSK9 Levels in Untreated Patients With Heterozygous or Homozygous Familial Hypercholesterolemia and the Response to High‐Dose Statin Therapy
Raal, F. J., Panz, V. R., Immelman, A., & Pilcher, G. J. (2013) · Journal of the American Heart Association · doi:10.1161/jaha.112.000028 · Cited by 135
Efficacy and safety of evolocumab (AMG 145), a fully human monoclonal antibody to PCSK9, in hyperlipidaemic patients on various background lipid therapies: pooled analysis of 1359 patients in four phase 2 trials
Stein, E. A., Giugliano, R. P., Koren, M. J., Raal, F. J., Roth, E. M., Weiss, R., Sullivan, D., Wasserman, S. M., Somaratne, R., Kim, J. B., et al. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu085 · Cited by 130
Regulation of low-density lipoprotein receptors: implications for pathogenesis and therapy of hypercholesterolemia and atherosclerosis
Goldstein, J. L., & Brown, M. S. (1987) · Circulation · doi:10.1161/01.cir.76.3.504 · Cited by 127
Self-Association of Human PCSK9 Correlates with Its LDLR-Degrading Activity
Fan, D., Yancey, P. G., Qiu, S., Ding, L., Weeber, E. J., Linton, M. F., & Fazio, S. (2008) · Biochemistry · doi:10.1021/bi7016359 · Cited by 107
Self-citation
Managing the underestimated risk of statin-associated myopathy
Rallidis, L. S., Fountoulaki, K., & ANASTASIOU‐NANA, M. I. (2011) · International Journal of Cardiology · doi:10.1016/j.ijcard.2011.07.048 · Cited by 99
A Two-step Binding Model of PCSK9 Interaction with the Low Density Lipoprotein Receptor
Yamamoto, T., Lu, C., & Ryan, R. O. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.199042 · Cited by 96
Furin-cleaved Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Is Active and Modulates Low Density Lipoprotein Receptor and Serum Cholesterol Levels
Lipari, M. T., Li, W., Moran, P., Kong-Beltran, M., Sai, T., Lai, J., Lin, S. J., Kolumam, G. A., Zavala‐Solorio, J., Izrael-Tomasevic, A., et al. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.380618 · Cited by 95
Loss of Plasma Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) After Lipoprotein Apheresis
Tavori, H., Giunzioni, I., Linton, M. F., & Fazio, S. (2013) · Circulation Research · doi:10.1161/circresaha.113.302655 · Cited by 87
Self-citation
Isolation and characterization of the circulating truncated form of PCSK9
Han, B., Eacho, P. I., Knierman, M. D., Troutt, J. S., Konrad, R. J., Yu, X., & Schroeder, K. M. (2014) · Journal of Lipid Research · doi:10.1194/jlr.m049346 · Cited by 73
Statins and ezetimibe modulate plasma proprotein convertase subtilisin kexin-9 (PCSK9) levels.
Davignon, J., & Dubuc, G. (2009) · PubMed Central · Cited by 72
The Type of LDLR Gene Mutation Predicts Cardiovascular Risk in Children with Familial Hypercholesterolemia
Guardamagna, O., Restagno, G., Rolfo, E., Pederiva, C., Martini, S., Abello, F., Baracco, V., Pisciotta, L., Pino, E., Calandra, S., et al. (2009) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2009.02.022 · Cited by 72
PCSK9 SNP rs11591147 is associated with low cholesterol levels but not with cognitive performance or noncardiovascular clinical events in an elderly population
Postmus, I., Trompet, S., de Craen, A. J. M., Buckley, B. M., Ford, I., Stott, D. J., Sattar, N., Slagboom, P. E., Westendorp, R. G. J., & Jukema, J. W. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m033969 · Cited by 67
Late-Breaking Clinical Trial Abstracts
Wilkins, L. (2002) · Circulation · doi:10.1161/01.cir.0000457464.79076.2c · Cited by 58
Recycling of Apolipoprotein E in Mouse Liver
Fazio, S., Linton, M. F., Hasty, A. H., & Swift, L. L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.12.8247 · Cited by 54
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Sasaki, M., Terao, Y., Ayaori, M., Uto-Kondo, H., Iizuka, M., Yogo, M., Hagisawa, K., Takiguchi, S., Yakushiji, E., Nakaya, K., et al. (2014) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.113.302670 · Cited by 28
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Research works printed but not linked: 3

Boston, 2014, Christopher P Cannon on behalf of the IMPROVE IT Investigators1 CD, Brigham and Womens Hosp. IMPROVE-IT trial: a comparison of ezetimibesimvastatin versus simvastatin monotherapy on cardiovascular outcomes after acute coronary syndrome., Circulation, 130, 2105
Blom, 2014, A 52-week placebo-controlled trial of evolocumab in hyperlipidemia., N Engl J Med, 370, 1809, 10.1056/NEJMoa1316222 · DOI · Paper page
Stein, 2013, Effect of the proprotein convertase subtilisinkexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia., Circulation, 128, 2113, 10.1161/CIRCULATIONAHA.113.004678 · DOI · Paper page

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Authors: Tavori, H., Giunzioni, I., & Fazio, S.
Affiliations: Oregon Health & Science University (US)
Corresponding author: Fazio, Sergio
ORCID: Tavori, Hagai
Fazio, Sergio
Venue: Current Opinion in Endocrinology, Diabetes & Obesity
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2015-04
Volume: 22
Issue: 2
Pages: 126-132
ISSN: 1752-296X (ISSN-L)
DOI: 10.1097/med.0000000000000137
PMC: PMC4384821
OpenAlex: W1995025365
Cited by: 30
References: 78
Citations by year: 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 5 · 2019: 4 · 2018: 4 · 2017: 3 · 2016: 5 · 2015: 2
FWCI: 0.89
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Current Opinion in Endocrinology Diabetes and Obesity (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Heart, Lung, and Blood Institute (R01HL106845)
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords: PCSK9 inhibition, PCSK9, PCSK9 monoclonal antibodies, LDL cholesterol lowering, LDL receptor, cholesterol metabolism, cardiovascular risk, lipoprotein(a), postprandial triglycerides, pleiotropy, statin therapy, patient selection
MeSH terms: Proprotein Convertase 9, Animals, Antibodies, Monoclonal, Hypolipidemic Agents, Cardiovascular Diseases, Humans, Receptors, LDL, Serine Endopeptidases, Signal Transduction, Serine Proteinase Inhibitors, Treatment Outcome, Proprotein Convertases, Dyslipidemias, Lipid Metabolism

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PCSK9 inhibition to reduce cardiovascular disease risk: recent findings from the biology of PCSK9

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