Utilidad para el tratamiento de las dislipemias graves
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Abstract
Loss-of-function ANGPTL3 variants are associated with beneficial effects on carbohydrate and lipid metabolism, and reduced risk of coronary heart disease.
The beneficial changes in lipid parameters obtained by ANGPTL3 inhibition together with atheroprotection observed in animal models and in epidemiological studies of human genetics make ANGPTL3 a new therapeutic target to prevent cardiovascular diseases. Two novel strategies have emerged to inhibit this protein: a monoclonal antibody and an antisense oligonucleotide, with the ability to significantly lower plasma cholesterol and triglycerides. Although the horizon is promising, we still do not know if the effects of a variant present from the beginning of life will be reproduced by the inhibition of this protein that takes place later in life through a pharmacological intervention.
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Elikir G, Cúneo C, Lorenzatti A, et al. Guía de práctica clínica de la Sociedad Argentina de Lípidos sobre diagnóstico y tratamiento de las dislipemias en adultos 2019 [Internet]. Buenos Aires: Sociedad Argentina de Lípidos; 2019 [consulta 2021 mayo 19]. Disponible en: https://www.sociedadargentinadelipidos.com/guias.
Gaudet D, Gipe DA, Pordy R, et al. ANGPTL3 inhibition in homozygous familial hypercholesterolemia. N Engl J Med. 2017;377(3):296-297. doi: 10.1056/NEJMc1705994. DOI: https://doi.org/10.1056/NEJMc1705994
Gaudet D, Gipe DA, Pordy R, et al. ANGPTL3 Inhibition in Homozygous Familial Hypercholesterolemia. N Engl J Med. 2017; 37783):296-297. doi: 10.1056/NEJMc1705994. DOI: https://doi.org/10.1056/NEJMc1705994
Gaudet D, Karwatowska-Prokopczuk E, Baum SJ, et al. Vupanorsen, an N-acetyl galactosamine-conjugated antisense drug to ANGPTL3 mRNA, lowers triglycerides and atherogenic lipoproteins in patients with diabetes, hepatic steatosis, and hypertriglyceridaemia. Eur Heart J. 2020;41(40):3936-3945. doi: 10.1093/eurheartj/ehaa689. DOI: https://doi.org/10.1093/eurheartj/ehaa689
Hegele RA, Boren J, Ginsberg HN, et al. Rare dyslipidaemias, from phenotype to genotype to management: a European Atherosclerosis Society task force consensus statement. Lancet Diabetes Endocrinol. 2020;8(1):50-67. doi: 10.1016/S2213-8587(19)30264-5. DOI: https://doi.org/10.1016/S2213-8587(19)30264-5
Minicocci I, Montali A, Robciuc MR, et al. Mutations in the ANGPTL3 gene and familial combined hypolipidemia: a clinical and biochemical characterization. J Clin Endocrinol Metab. 2012;97(7):e1266-1275. doi: 10.1210/jc.2012-1298. DOI: https://doi.org/10.1210/jc.2012-1298
Musunuru K, Pirruccello JP, Do R, et al. Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia. N Engl J Med. 2010;363(23):2220-2227. doi: 10.1056/NEJMoa1002926. DOI: https://doi.org/10.1056/NEJMoa1002926
Reeskamp LF, Millar JS, Wu L, et al. ANGPTL3 inhibition with Evinacumab results in faster clearance of IDL and LDL apoB in patients with homozygous familial hypercholesterolemia. Arterioscler Thromb Vasc Biol. 2021;41(5):1753-1759. doi: 10.1161/ATVBAHA.120.315204. DOI: https://doi.org/10.1161/ATVBAHA.120.315204
Rosenson RS, Burgess LJ, Ebenbichler CF, et al. Evinacumab in patients with refractory hypercholesterolemia. N Engl J Med. 2020;383(24):2307-2319. doi: 10.1056/NEJMoa2031049. DOI: https://doi.org/10.1056/NEJMoa2031049
Zhang R. The ANGPTL3-4-8 model, a molecular mechanism for triglyceride trafficking. Open Biol. 2016;6:150272-150282. doi: 10.1098/rsob.150272. DOI: https://doi.org/10.1098/rsob.150272