Mecanismos fisiopatologicos de la dislipidemia

Cristhián Jerez Fernández; Javiera  Irribarren Bravo; Fernanda Diaz Urbina; Jovanka  Kusanovic Blanco; Brayan Araya Zumaran

doi:10.22490/24629448.6882

Vol. 21 Núm. 40 (2023)

Publicado

2023-05-01

PDF

Métricas

Cargando métricas ...

Mecanismos fisiopatologicos de la dislipidemia

DOI: https://doi.org/10.22490/24629448.6882

Sección

Artículo de Revisión

Cristhián Jerez Fernández Universidad del Alba

Javiera Irribarren Bravo Universidad del Alba, Santiago de Chile

Fernanda Diaz Urbina Universidad del Alba

Jovanka Kusanovic Blanco Universidad del Alba

Brayan Araya Zumaran Universidad del Alba

La dislipidemia corresponde a una alteración de los lípidos en el plasma, lo que significa un aumento de colesterol y/o triglicéridos plasmáticos. Objetivos. Describir los mecanismos fisiopatológicos detrás de la dislipidemia y determinar cómo estos se aplican a los tratamientos. Metodología. Tras una búsqueda bibliográfica exhaustiva de 85 estudios publicados hasta el año 2011, se identificaron los aspectos más importantes tanto de la fisiología, fisiopatología, complicaciones y terapéuticas de esta patología. Resultados. Los mecanismos fisiopatológicos de la dislipidemia se subdividen en mecanismos primarios y secundarios. El tratamiento de la dislipidemia consta de terapias farmacológicas y no farmacológicas, incluyendo en estos últimos, cambios en el estilo de vida que modifiquen la dieta y el ejercicio físico. Dentro de las terapias farmacológicas, se han estudiado a lo largo del tiempo múltiples fármacos y sus interacciones al combinar con otros de estos, siendo los mecanismos más estudiados la inhibición de la síntesis endógena de colesterol, inhibición de la degradación del receptor de LDL, inhibición de la absorción del colesterol, atrapamiento de los ácidos biliares, disminución de la síntesis de lipoproteínas de muy baja densidad y síntesis de triglicéridos. Conclusión.
La dislipidemia se conoce actualmente a nivel más molecular, su correcta compresión nos permite tomar mejores decisiones terapéuticas.

hiperlipidemias, hipertrigliceridemia, hipercolesterolemia, factores de riesgo de enfermedad cardiaca, pancreatitis, nticolesterolemiantes

Departamento de Epidemiologia, Division de Planificación Sanitaria S de SP. Encuesta nacional de salud 2016- 2017 Segunda entrega de resultados. Ens 2016-2017.018;(Encuesta Nacional de Salud):50. http://www.ipsuss.cl/ipsuss/site/artic/20171122/asocfile/20171122142253/ens_2016_17_primeros_resultados.pdf

Martin ISM, Yurrita LC, Jose Ciudad Cabanas M, Angeles Cuadrado Cenzual M, Cabria MH, Elisa Calle Puron M. Manejo del riesgo de enfermedad cardiovascular con leche enriquecida en esteroles en población joven adulta; ensayo clínico controlado aleatorizado y cruzado. Nutr Hosp. 2014;30(4):945-951. doi:10.3305/nh.2014.30.4.7654

Pa CK. The effective history of critical theory: The reception history of Frankfurt school in Taiwan. Universitas (Stuttg). 2010;37(6):111-125.

WHO. Global Status Report on Noncommunicable Diseases 2014 (http://apps.who.int/medicinedocs/es/m/abstract/Js21756en/). Geneva World Heal Organ. Published online 2014.

Vaziri ND. Disorders of lipid metabolism in nephrotic syndrome: mechanisms and consequences. Kidney Int. 2016;90(1):41-52. doi:10.1016/j.kint.2016.02.026

Santos-Gallego CG, Badimón JJ. Papel de la proteína trasferidora de ésteres de colesterol en aterosclerosis: más preguntas que respuestas, más dudas que promesas. Rev Colomb Cardiol. 2012;19(4):180-183. doi:10.1016/s0120-5633(12)70128-6

Goldstein JL, Brown MS. The LDL receptor. Arterioscler Thromb Vasc Biol. 2009;29(4):431-438. doi:10.1161/ATVBAHA.108.179564

Alphonse PAS, Jones PJH. Revisiting Human Cholesterol Synthesis and Absorption: The Reciprocity Paradigm and its Key Regulators. Lipids. 2016;51(5):519-536. doi:10.1007/s11745-015-4096-7

Stein EA, Mellis S, Yancopoulos GD. Effect of a Monoclonal Antibody to PCSK9 on LDL Cholesterol. N Engl J Med. 2012 Mar 22;366(12):1108-18. doi: 10.1056/NEJMoa1105803.

Shapiro MD, Minnier J, Tavori H, et al. Relationship between low-density lipoprotein cholesterol and lipoprotein(A) lowering in response to PCSK9 inhibition with evolocumab. J Am Heart Assoc. 2019;8(4). doi:10.1161/JAHA.118.010932

Lin X, Racette SB, Ma L, Wallendorf M, Ostlund RE. Ezetimibe increases endogenous cholesterol excretion in humans. Arterioscler Thromb Vasc Biol. 2017;37(5):990- 996. doi:10.1161/ATVBAHA.117.309119

Okour M, Brigandi RA, Tenero D. A population analysis of the DGAT1 inhibitor GSK3008356 and its effect on endogenous and meal-induced triglyceride turnover in healthy subjects. Fundam Clin Pharmacol. 2019;33(5):567- 580. doi:10.1111/fcp.12455

Gidding SS, Champagne MA, De Ferranti SD, et al. The Agenda for Familial Hypercholesterolemia: A Scientific Statement from the American Heart Association. Circulation. 2015;132(22):2167-2192. doi:10.1161/CIR.0000000000000297

Futema M, Plagno V, Li KW, et al. Whole exome sequencing of familial hypercholesterolaemia patients negative for LDLR/APOB/PCSK9 mutations. J Med Genet. 2014;51(8):537- 544. doi:10.1136/jmedgenet-2014-102405

Richard C, Couture P, Desroches S, et al. Effect of the Mediterranean diet with and without weight loss on surrogate markers of cholesterol homeostasis in men with the metabolic syndrome. Br J Nutr. 2012;107(5):705-711. doi:10.1017/S0007114511003436

Tavori H, Fan D, Blakemore JL, et al. Serum proprotein convertase subtilisin/kexin type 9 and cell surface low-density lipoprotein receptor evidence for a reciprocal regulation. Circulation. 2013;127(24):2403-2413. doi:10.1161/CIRCULATIONAHA.113.001592

Reyes-Soffer G, Pavlyha M, Ngai C, et al. Effects of PCSK9 inhibition with alirocumab on lipoprotein metabolism in healthy humans. Circulation. 2017;135(4):352-362. doi:10.1161/CIRCULATIONAHA.116.025253

Chora JR, Medeiros AM, Alves AC, Bourbon M. Analysis of publicly available LDLR, APOB, and PCSK9 variants associated with familial hypercholesterolemia: Application of ACMG guidelines and implications for familial hypercholesterolemia diagnosis. Genet Med. 2018;20Chora, J(6):591-598. doi:10.1038/gim.2017.151

Westerterp M, Murphy AJ, Wang M, et al. Deficiency of ATP-binding cassette transporters a1 and g1 in macrophages increases inflammation and accelerates atherosclerosis in mice. Circ Res. 2013;112(11):1456-1465. doi:10.1161/CIRCRESAHA.113.301086

Suehiro T, Ikeda Y. Tangier disease. Nippon rinsho Japanese J Clin Med. 2012;65 Suppl 7(5):604-607.

He X. Sitosterolemia : Inherited Disorder of Plant Sterols Absorption and Biliary Excretion. :4-6.

Hegele RA, Berberich AJ, Ban MR, et al. Clinical and biochemical features of different molecular etiologies of familial chylomicronemia. J Clin Lipidol. 2018;12(4):920- 927.e4. doi:10.1016/j.jacl.2018.03.093

Surendran RP, Visser ME, Heemelaar S, et al. Mutations in LPL, APOC2, APOA5, GPIHBP1 and LMF1 in patients with severe hypertriglyceridaemia. J Intern Med. 2012;272(2):185- 196. doi:10.1111/j.1365-2796.2012.02516.x

Voss C V., Davies BSJ, Tat S, et al. Mutations in lipoprotein lipase that block binding to the endothelial cell transporter GPIHBP1. Proc Natl Acad Sci U S A. 2011;108(19):7980-7984. doi:10.1073/pnas.1100992108

Rios JJ, Shastry S, Jasso J, et al. Deletion of GPIHBP1 causing severe chylomicronemia. J Inherit Metab Dis. 2012;35(3):531-540. doi:10.1007/s10545-011-9406-5

Goulbourne CN, Gin P, Tatar A, et al. The GPIHBP1-LPL complex is responsible for the margination of triglyceriderich lipoproteins in capillaries. Cell Metab. 2014;19(5):849- 860. doi:10.1016/j.cmet.2014.01.017

Oliva CP, Carubbi F, Schaap FG, Bertolini S, Calandra S. Hypertriglyceridaemia and low plasma HDL in a patient with apolipoprotein A-V deficiency due to a novel mutation in the APOA5 gene. J Intern Med. 2008;263(4):450-458. doi:10.1111/j.1365-2796.2007.01912.x

Merkel M, Loeffler B, Kluger M, et al. Apolipoprotein AV accelerates plasma hydrolysis of triglyceride-rich lipoproteins by interaction with proteoglycan-bound lipoprotein lipase. J Biol Chem. 2005;280(22):21553-21560. doi:10.1074/jbc.M41141220029. Ahmad Z, Banerjee P, Hamon S, et al. Inhibition of Angiopoietin-Like Protein 3 with a Monoclonal Antibody Reduces Triglycerides in Hypertriglyceridemia. Circulation. 2019;140(6):470-486. doi:10.1161/CIRCULATIONAHA.118.039107

Gaudet D, Brisson D, Tremblay K, et al. Targeting APOC3 in the Familial Chylomicronemia Syndrome. N Engl J Med. 2014;371(23):2200-2206. doi:10.1056/nejmoa1400284

Jung KY, Ahn HY, Han SK, Park YJ, Cho BY, Moon MK. Association between thyroid function and lipid profiles, apolipoproteins, and high-density lipoprotei1. Jung KY, Ahn HY, Han SK, Park YJ, Cho BY, Moon MK. Association between thyroid function and lipid profiles, apolipoproteins, and high-density lipoprote. J Clin Lipidol. 2017;11(6):1347-1353. doi:10.1016/j.jacl.2017.08.015

Bonde Y, Breuer O, Lütjohann D, Sjöberg S, Angelin B, Rudling M. Thyroid hormone reduces PCSK9 and stimulates bile acid synthesis in humans. J Lipid Res. 2014;55(11):2408-2415. doi:10.1194/jlr.M051664

Pavlic M, Xiao C, Szeto L, Patterson BW, Lewis GF. Insulin acutely inhibits intestinal lipoprotein secretion in humans in part by suppressing plasma free fatty acids. Diabetes. 2010;59(3):580-587. doi:10.2337/db09-1297

Nogueira JP, Maraninchi M, Béliard S, et al. Absence of acute inhibitory effect of insulin on chylomicron production in type 2 diabetes. Arterioscler Thromb Vasc Biol. 2012;32(4):1039- 1044. doi:10.1161/ATVBAHA.111.242073

Caron S, Verrijken A, Mertens I, et al. Transcriptional activation of apolipoprotein CIII expression by glucose may contribute to diabetic dyslipidemia. Arterioscler Thromb Vasc Biol. 2011;31(3):513-519. doi:10.1161/ATVBAHA.110.220723

Kathiresan S, Otvos JD, Sullivan LM, et al. Increased small low-density lipoprotein particle number: A prominent feature of the metabolic syndrome in the Framingham Heart Study. Circulation. 2006;113(1):20-29. doi:10.1161/CIRCULATIONAHA.105.567107

Ruggenenti P, Mise N, Pisoni R, et al. Diverse effects of increasing lisinopril doses on lipid abnormalities in chronic nephropathies. Circulation. 2003;107(4):586-592. doi:10.1161/01.CIR.0000047526.08376.80

Vaziri ND, Yuan J, Ni Z, Nicholas SB, Norris KC. Lipoprotein lipase deficiency in chronic kidney disease is accompanied by down-regulation of endothelial GPIHBP1 expression. Clin Exp Nephrol. 2012;16(2):238-243. doi:10.1007/s10157-011-0549-3

Liu S, Vaziri ND. Role of PCSK9 and IDOL in the pathogenesis of acquired LDL receptor deficiency and hypercholesterolemia in nephrotic syndrome. Nephrol Dial Transplant. 2014;29(3):538-543. doi:10.1093/ndt/gft439

Lafferty MJ, Bradford KC, Erie DA, Neher SB. Angiopoietin-like protein 4 inhibition of lipoprotein lipase: Evidence for reversible complex formation. J Biol Chem. 2013;288(40):28524-28534. doi:10.1074/jbc.M113.497602

Zhang Y, Hong JY, Rockwell CE, Copple BL, Jaeschke H, Klaassen CD. Effect of bile duct ligation on bile acid composition in mouse serum and liver. Liver Int. 2012;32(1):58-69. doi:10.1111/j.1478-3231.2011.02662.x

Ferslew BC, Xie G, Johnston CK, et al. Altered Bile Acid Metabolome in Patients with Nonalcoholic Steatohepatitis. Dig Dis Sci. 2015;60(11):3318-3328. doi:10.1007/s10620-015-3776-8

Bechmann LP, Kocabayoglu P, Sowa JP, et al. Free fatty acids repress small heterodimer partner (SHP) activation and adiponectin counteracts bile acid-induced liver injury in superobese patients with nonalcoholic steatohepatitis. Hepatology. 2013;57(4):1394-1406. doi:10.1002/hep.26225

Yu L, Hammer RE, Li-Hawkins J, et al. Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion. Proc Natl Acad Sci U S A. 2002;99(25):16237-16242. doi:10.1073/pnas.252582399

Gylling H, Miettinen TA. Cholesterol absorption, synthesis, and LDL metabolism in NIDDM. Diabetes Care. 1997;20(1):90-95. doi:10.2337/diacare.20.1.90

Clemente-Postigo M, Queipo-Ortuño MI, Fernandez-Garcia D, Gomez-Huelgas R, Tinahones FJ, Cardona F. Adipose tissue gene expression of factors related to lipid processing in obesity. PLoS One. 2011;6(9):3-10. doi:10.1371/journal.pone.0024783

Mudráková E, Poledne R, Kovář J. Postprandial triglyceridemia after single dose of alcohol in healthy young men. Nutr Metab Cardiovasc Dis. 2013;23(3):183-188. doi:10.1016/j.numecd.2011.05.003

Zemánková K, Makoveichuk E, Vlasáková Z, Olivecrona G, Kovář J. Acute alcohol consumption downregulates lipoprotein lipase activity in vivo. Metabolism. 2015;64(11):1592-1596. doi:10.1016/j.metabol.2015.08.016

Zhong W, Zhao Y, Tang Y, et al. Chronic alcohol exposure stimulates adipose tissue lipolysis in mice: Role of reverse triglyceride transport in the pathogenesis of alcoholic steatosis. Am J Pathol. 2012;180(3):998-1007. doi:10.1016/j.ajpath.2011.11.017

Formisano E, Pasta A, Cremonini AL, et al. Efficacy of Nutraceutical Combination of Monacolin K, Berberine, and Silymarin on Lipid Profile and PCSK9 Plasma Level in a Cohort of Hypercholesterolemic Patients. J Med Food. 2020;23(6):658-666. doi:10.1089/jmf.2019.0168

Santovito D, Marcantonio P, Mastroiacovo D, et al. High dose rosuvastatin increases ABCA1 transporter in human atherosclerotic plaques in a cholesterol-independent fashion. Int J Cardiol. 2020;299(xxxx):249-253. doi:10.1016/j.ijcard.2019.07.094

Murphy AA, Palinski W, Rankin S, Morales AJ, Parthasarathy S. Macrophage scavenger receptor(s) and oxidatively modified proteins in endometriosis. Fertil Steril. 1998;69(6):1085- 1091. doi:10.1016/S0015-0282(98)00088-0

Engelbert AK, Soukup ST, Roth A, et al. Isoflavone supplementation in postmenopausal women does not affect leukocyte LDL receptor and scavenger receptor CD36 expression: A double-blind, randomized, placebocontrolled trial. Mol Nutr Food Res. 2016;60(9):2008-2019.doi:10.1002/mnfr.201600019

Gao S, Zhao D, Wang M, et al. Association Between Circulating Oxidized LDL and Atherosclerotic Cardiovascular Disease: A Meta-analysis of Observational Studies. Can J Cardiol. 2017;33(12):1624-1632. doi:10.1016/j.cjca.2017.07.015

Wang L, Tao L, Hao L, et al. A moderate-fat diet with one avocado per day increases plasma antioxidants and decreases the oxidation of small, dense LDL in adults with overweight and obesity: A randomized controlled trial. J Nutr. 2020;150(2):276-284. doi:10.1093/jn/nxz231

Song G, Lin Q, Zhao H, et al. Hydrogen activates atpbinding cassette transporter a1-dependent efflux ex vivo and improves high-density lipoprotein function in patients with hypercholesterolemia: A double-blinded, randomized, and placebo-controlled trial. J Clin Endocrinol Metab. 2015;100(7):2724-2733. doi:10.1210/jc.2015-1321

Libby P, Buring JE, Badimon L, et al. Atherosclerosis. Nat Rev Dis Prim. 2019;5(1):1-18. doi:10.1038/s41572-019-0106-z

Watts GF, Ooi EMM, Chan DC. Demystifying the management of hypertriglyceridaemia. Nat Rev Cardiol. 2013;10(11):648-661. doi:10.1038/nrcardio.2013.140

Peng J, Luo F, Ruan G, Peng R, Li X. Hypertriglyceridemia and atherosclerosis. Lipids Health Dis. 2017;16(1). doi:10.1186/s12944-017-0625-0

Kyriakidis A V., Karydakis P, Neofytou N, et al. Plasmapheresis in the management of acute severe hyperlipidemic pancreatitis: Report of 5 cases. Pancreatology. 2005;5(2-3):201-204. doi:10.1159/000085272

Noel P, Patel K, Durgampudi C, et al. Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections. Gut. 2016;65(1):100-111.doi:10.1136/gutjnl-2014-308043

Navina S, Acharya C, DeLany JP, et al. Lipotoxicity causes multisystem organ failure and exacerbates acute pancreatitis in obesity. Sci Transl Med. 2011;3(107). doi:10.1126/scitranslmed.3002573

Acharya C, Navina S, Singh VP. Role of pancreatic fat in the outcomes of pancreatitis. Pancreatology. 2014;14(5):403- 408. doi:10.1016/j.pan.2014.06.004

Zádori N, Gede N, Antal J, et al. EarLy Elimination of Fatty Acids iN hypertriglyceridemia-induced acuTe pancreatitis (ELEFANT trial): Protocol of an open-label, multicenter, adaptive randomized clinical trial. Pancreatology. 2020;20(3):369-376. doi:10.1016/j.pan.2019.12.018

Patel K, Trivedi RN, Durgampudi C, et al. Lipolysis of visceral adipocyte triglyceride by pancreatic lipases converts mild acute pancreatitis to severe pancreatitis independent of necrosis and inflammation. Am J Pathol. 2015;185(3):808- 819. doi:10.1016/j.ajpath.2014.11.019

Vincent MJ, Allen B, Palacios OM, Haber LT, Maki KC. Meta-regression analysis of the effects of dietary cholesterol intake on LDL and HDL cholesterol. Am J Clin Nutr. 2019;109(1):7-16. doi:10.1093/ajcn/nqy273

Bhutani S, Klempel MC, Kroeger CM, Trepanowski JF, Varady KA. Alternate day fasting and endurance exercise combine to reduce body weight and favorably alter plasma lipids in obese humans. Obesity. 2013;21(7):1370-1379. doi:10.1002/oby.20353

Guo W, Kawano H, Piao L, Itoh N, Node K, Sato T. Effects of aerobic exercise on lipid profiles and high molecular weight adiponectin in Japanese workers. Intern Med. 2011;50(5):389- 395. doi:10.2169/internalmedicine.50.4380

Robinson JG, Nedergaard BS, Rogers WJ, et al. Effect of evolocumab or ezetimibe added to moderate- Or highintensity statin therapy on LDL-C lowering in patients with hypercholesterolemia: The LAPLACE-2 randomized clinical trial. JAMA - J Am Med Assoc. 2014;311(18):1870-1882. doi:10.1001/jama.2014.4030

Chou R, Dana T, Blazina I, Daeges M, Jeanne TL. Statins for prevention of cardiovascular disease in adults: Evidence report and systematic review for the US preventive services task force. JAMA - J Am Med Assoc. 2016;316(19):2008- 2024. doi:10.1001/jama.2015.15629

Chen F, Maridakis V, O’Neill EA, et al. The effects of simvastatin treatment on plasma lipid-related biomarkers in men with dyslipidaemia. Biomarkers. 2011;16(4):321-333. doi:10.3109/1354750X.2011.561367

Qu H, Guo M, Chai H, Wang WT, Ga ZY, Shi DZ. Effects of coenzyme Q10 on statin-induced myopathy: An updated meta-analysis of randomized controlled trials. J Am Heart Assoc. 2018;7(19):1-11. doi:10.1161/JAHA.118.009835

Brønden A, Mikkelsen K, Sonne DP, Hansen M, Våben C, Gabe MN, Rosenkilde M, Tremaroli V, Wu H, Bäckhed F, Rehfeld JF, Holst JJ, Vilsbøll T, Knop FK. Glucose-lowering effects and mechanisms of the bile acid-sequestering resin sevelamer. Diabetes Obes Metab. 2018 Jul;20(7):1623- 1631. doi: 10.1111/dom.13272. Epub 2018 Mar 26. PMID: 29493868.

Sahebkar A, Simental-Mendía LE, Watts GF, Golledge J. Impact of fibrate therapy on plasma plasminogen activator inhibitor-1: A systematic review and meta-analysis of randomized controlled trials. Atherosclerosis. 2015;240(1):284-296. doi:10.1016/j.atherosclerosis.2015.03.016

Lauring B, Taggart AKP, Tata JR, et al. Niacin lipid efficacy is independent of both the niacin receptor GPR109A and free fatty acid suppression. Sci Transl Med. 2012;4(148). doi:10.1126/scitranslmed.3003877

Hu M, Chu WCW, Yamashita S, et al. Liver fat reduction with niacin is influenced by DGAT-2 polymorphisms in hypertriglyceridemic patients. J Lipid Res. 2012;53(4):802- 809. doi:10.1194/jlr.P023614

Ginsberg HN, Reyes-Soffer G. Niacin: A long history, but a questionable future. Curr Opin Lipidol. 2013;24(6):475- 479. doi:10.1097/MOL.0000000000000017

Casanova MA, Medeiros F, Trindade M, Cohen C, Oigman W, Neves MF. Omega-3 fatty acids supplementation improves endothelial function and arterial stiffness in hypertensive patients with hypertriglyceridemia and high cardiovascular risk. J Am Soc Hypertens. 2017;11(1):10-19. doi:10.1016/j.jash.2016.10.004

Kim CH, Han KA, Yu J, et al. Efficacy and Safety of Adding Omega-3 Fatty Acids in Statin-treated Patients with Residual Hypertriglyceridemia: ROMANTIC (Rosuvastatin- OMAcor iN residual hyperTrIglyCeridemia), a Randomized, Double-blind, and Placebo-controlled Trial. Clin Ther. 2018;40(1):83-94. doi:10.1016/j.clinthera.2017.11.007

Stroes ESG, Susekov A V., de Bruin TWA, Kvarnström M, Yang H, Davidson MH. Omega-3 carboxylic acids in patients with severe hypertriglyceridemia: EVOLVE II, a randomized, placebo-controlled trial. J Clin Lipidol. 2018;12(2):321- 330. doi:10.1016/j.jacl.2017.10.012

Sahebkar A, Simental-Mendía LE, Watts GF, Serban MC, Banach M. Comparison of the effects of fibrates versus statins on plasma lipoprotein(a) concentrations: A systematic review and meta-analysis of head-to-head randomized controlled trials. BMC Med. 2017;15(1):1-14. doi:10.1186/s12916-017-0787-7

Franco D, Henao Y, Monsalve M, Gutiérrez F, Hincapie J, Amariles P. Interacciones medicamentosas de agentes hipolipemiantes: Aproximación para establecer y valorar su relevancia clínica. Revisión estructurada. Farm Hosp. 2013;37(6):539-557. doi:10.7399/FH.2013.37.6.1077

Giugliano RP, Desai NR, Kohli P, et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACETIMI 57): A randomised, placebo-controlled, doseranging, phase 2 stu. Lancet. 2012;380(9858):2007-2017.doi:10.1016/S0140-6736(12)61770-X

Welder G, Zineh I, Pacanowski MA, Troutt JS, Cao G, Konrad RJ. High-dose atorvastatin causes a rapid sustained increase in human serum PCSK9 and disrupts its correlation with LDL cholesterol. J Lipid Res. 2010;51(9):2714-2721. doi:10.1194/jlr.M008144

Jerez Fernández, C., Irribarren Bravo, J., Diaz Urbina, F., Kusanovic Blanco, J., & Araya Zumaran, B. (2023). Mecanismos fisiopatologicos de la dislipidemia. Nova, 21(40), 11-39. https://doi.org/10.22490/24629448.6882

Descargar cita

Derechos de autor 2023 Nova

Esta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial-SinDerivadas 4.0.

Publicado

Mecanismos fisiopatologicos de la dislipidemia

Declaración de privacidad.

Palabras clave