Publicado

2006-01-01

Apolipoproteína E y enfermedad cardiovascular

Apolipoprotein E and cardiovascular disease

Palabras clave:

polipoproteína, lipoproteína, polimorfismo (genético), arteriosclerosis coronaria. (es)
apolipoprotein, lipoprotein, polymorphism (genetic), coronary arteriosclerosis (en)

Descargas

Autores/as

  • Adriana Moreno Valladares MSc, Docente Investigador,Universidad Colegio Mayor de Cundinamarca. Facultad Ciencias de la Salud.
  • Álvaro Cartagena Perdomo MD, Grupo de Medicina Interna y Cardiología,Hospital San Blas.Profesor Asistente, Facultad de Medicina Universidad Nacional de Colombia
  • Guillermo Mora Pabón MD,Profesor Asociado, Facultad de Medicina Universidad Nacional de Colombia

La apolipoproteína E es una glicoproteína polimórfica que interactúa con los receptores de lipoproteínas (LRP-Receptor Related Protein) o receptores ApoE y los receptores de lipoproteínas de baja densidad (receptores LDL). Cuando las lipoproteínas se unen al receptor comienza la captación y degradación de lípidos por parte de la célula, lo que permite la utilización del colesterol contenido en las lipoproteínas, produciéndose una autorregulación intracelula.r

La tres isoformas de mayor importancia de ApoE se denominan Apo E2, E3 y E4 y son producto de tres alelos e2, e3, e4 de un gen único. Este factor está relacionado con la cantidad de lipoproteínas que contienen ApoE para receptores E⁄B. El menor contenido de lipoproteínas con ApoE puede aumentar la actividad del receptor LDL y consecuentemente, bajar la concentración de LDL en circulación. De otra parte, las partículas con Apo E3 o Apo E4, causan disminución de la regulación de receptores LDL y producen elevación del LDL plasmático.

Muchos estudios en poblaciones humanas han demostrado la relación entre este polimorfismo de apoE y la variación en los niveles plasmáticos de lípidos y de lipoproteínas y el riesgo de desarrollar enfermedad cardiovascular.

La enfermedad cardiovascular es el resultado de la interacción de diferentes factores entre los que se encuentra el factor genético y específicamente el polimorfismo de la ApoE. La presencia del alelo e4 de la ApoE puede explicar, en parte, la mayor frecuencia de enfermedad cardiovascular en quienes lo portan

Apolipoprotein E is a polymorphic glycoprotein who interacts with the lipoprotein receptors (LRP-Receptor Related Protein) and the receptors for low density lipoproteins of (LDL receptors). When lipoproteins bring up the receptors begins lipids captation and degradation which allows cholesterol utilization, taking place an intracellular auto regulation.

The three isoforms of greater importance: Apo E2, E3 and E4 are product of three alleles e2, e3, e4 of one only gene. This factor is related with the amount of lipoproteins that contains ApoE for E/B receptors.

A low concentration of lipoproteins with ApoE can increase the activity of LDL receptors and consequently downward the circulating LDL. In the other hand particles with Apo E3 or Apo E4, can cause a downward regulation of LDL and in this way produces a LDL plasma elevation.

Many studies in human populations have concluded that this polymorphism of apoE and the plasma variation of lipoproteins are associated with cardiovascular risk.

Cardiovascular disease is the result of different interaction between factors which are genetic factor specially ApoE polymorphism e4 allelic of ApoE can explain, in some degree, the greater frequency of cardiovascular disease in those who carries it.

Referencias

Ministerio de Salud, Grupo de Vigilancia en Salud Pública. Causas de Mortalidad en Colombia por departamento según grupo de causas, 1999. In DANE. Archivos de defunciones.2001.

Ministerio de Salud, Grupo de Vigilancia en Salud Pública. Mortalidad por grupo etáreo según causas, Colombia 1999, DANE. Archivos defunciones, Bogotá.2001.

Argentina Ministerio de Salud. 1995. Estudio de Carga de Enfermedad.

Ministerio Nacional de Salud, Instituto Colombiano de Educación Superior I.Especialidades Medico Quirúrgicas en Medicina. In Informe Consolidado 2002-2003, Asociación Colombiana de Facultades de Medicina (ASCOFAME). 2004.Bogotá

Villa-Colinayo VJ, Shi WJ, Araujo JJ, Lusis AJ. Genetics of atherosclerosis: The Search for genes Acting at level of the vessel wall. Current Atherosclerosis Report 2;2000:380-389

Martínez J, González V, Cortés L, Badimon L. Biología Molecular y Celular de las lesiones ateroscleróticas. Rev Esp Cardiol 2001;54: 218-231

Von Eckardstein A, Roch Nofer J, Assman G. High density lipoproteins and arteriosclerosis. Role of cholesterol efflux and reverse cholesterol transport. Arteriosclerosis Thrombosis Vascular Biology 2001;21:13-27

Sánchez M. Patología Molecular de la HDL. Ars Pharmaceutica 2000;41: 59-65

Davignon J, Gregg RE, Sing CF. Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis 1988;8: 1-21

Ilveskoski E, Perola M, Lehtimaki T, et al. Age-dependent association of apolipoprotein E genotype with coronary and aortic atherosclerosis in middle-aged men: an autopsy study. Circulation 1999;100: 608-613

Batalla. Apolipoprotein E genotype and coronary heart disease. J Am Coll Card 2001;37: 329-330

Kolovou G, Daskalova D, Mikhailidis DP. Apolipoprotein E polymorphism and atherosclerosis. Angiology 2003;54: 59-71

Fernandez Miranda C, Aranda JL, Martin MA, Arenas J, Nunez V, Gomez de la Camara A. Apolipoprotein E polymorphism and carotid atherosclerosis in patients with coronary disease. Int J Cardiol.2004; 94: 209-212

Scanu AM, Landsberger FR. Lipoprotein Structure. Acad Sci 1980;348: 1-436

Gotto AM, Pownall HJ, Havel RJ. Introduction to the plasma lipoproteins. Methods Enzymol 1986;128: 3-41

Segrest JP, Jackson RL, Morriset JD. A molecular theory of lipid protein interactions in the plasma lipoproteins. FEBS Lett 1974; 38: 247-53

Segrest JP, Garber DW, Brouillette CG. Tha amphipathic alfa helix: a multifuncional structural motif in plasma lipoprotein. Ad Protein Chem 1994;45: 303-369

Brown MS, Kovanen PT, Goldstein JL. Receptor mediated uptake of lipoprotein -cholesterol and its utilization for steroid synthesis in the adrenal cortex. Recent Prog Horm Res 1979;35: 215-231

Windler E, Chao YS, Havel RJ. Determinants of hepatics uptake to the triglyceride-rich lipoproteins and their remnants in the rat. J Biol Chem 1980;255: 5475-5480

Glomset F. Tha plasma lecithin: Cholesterol acyltransferase reaction. J Lipid Res 1968; 9: 155-167

Hahn PF. Abolishment of alimentary lipemia following injection of heparin. Science 1943; 98: 19

Luo CC, Li WH, Moore MN. Structure and evolution of the apolipoprotein multigene family. J Mol Biol 1986; 187: 325-340.

Tripathi B, Rajavashisth JS, Kaprein KL, Reue A, Lusis J. Evolution of apolipoprotein E: Mouse sequence and evidence for an 11-nucleotide ancestral unit. Proc. Nadl. Acad. Sci 1985; 82: 8085-8089

Rall Jr SC, Weisgraber KH, Innerarity TL, Mahely RW. Structural basis for receptor binding hetrogeneity of Apolipoprotein E from type III hyperlipoproteinemic subjects. Genetics 1982;79: 4695-4700

Shore B, Shore VG. Heterogeneity of human plasma very low density lipoproteins: Separation of species differing in protein components. Biochemistry 1973;12: 502-507

Gamboa R, Hernandéz G, Ramiro P, Zuñiga J, Granados J. Polimorfismo de la Apolipoproteina E y sus asociaciones con enfermedad cardiovascular. Arch Inst Cardiol Mex 1999; 69: 375-382

Mahley RW. Apolipoprotein E: Cholesterol transport protein with expanding role in the celll biology. Science 1988;240: 622-630

Ginsberg HN. Lipoprotein physiology. Endocrinol Metab Clin North Am 1998;27: 503-519

Francke U, Brown MS, Goldstei JL. Assignament of the human gene for the low density lipoprotein receptor tochromosome 10: syntesis for a receptor, a ligando, and a genetics diseases. Proc Natl Acad Sci USA 1984;81: 2826-2830

Pham T, Kodvawala A, Hui DY. The receptor binding domain of apolipoprotein E is responsible for its antioxidant activity. Biochemistry 2005;44: 777-7582

Wilson C, Wardell MR, Weisgraber KH, Mahley RW, Agard DA. Three-dimensional structure of the LDL receptor-binding doamin of human apolipoprotein E. Science 1991;252: 1817-1822

Weisgraber KH, Innerarity TL, Rall Jr SC, Mahley RW. Receptor interactions controlling lipoprotein metabolism. Can J Biochem Cell Biol 1985;63: 898-905

Shelburne FA, Quartford SH. A new apoprotein of human plasma very low density lipoproteins. J Biol Chem 1974; 249: 1428-1433

Zannis VI, McPherson J, Golberg G, Karathanasis SK, Breslow JL. Synthesis, intracellular processing and signal peptide of human apolipoprotein E. J Biol Chem 1984; 259: 5495-5499

Wetterau JR, Aggerbeck LP, Rall Jr SC, Weisgraber KH. Human apolipoprotein E3 in aqueous solution. I. Evidence for two structural domains. J Biol Chem. 1988;263: 6240-6248

Aggerbeck LP, Wetterau JR, Weisgraber KH, Wu C S, Lindgren FT. Human apolipoprotein E3 in aqueous solution. II. Properties of the amino- and carboxyl-terminal domains. J Biol Chem 1988; 263: 6249-6258

Weisgraber KH. Apolipoprotein E distribution among human plasma lipoprotein: role of the Cysteine-arginine interchange at residuo 112. J Lipid Res 1990;31: 1503-1511

Shore VG, Shore B. Biochemistry. In 1973; 12: 502-507

Myklebost O, Rogne S. A physical map of the apoprotein gene cluster on human chromosome 19. Hum Genet 1988;28: 244-247

Hixson JE, Vernier DT. Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res 1990;31: 545-548

Zannis VI, Breslow JL, San-Giacomo TR, Aden DP, Knowles BB. Characterization of the major apolipoproteins secreted by two human hepatoma cell lines. Biochemistry 1981; 20: 7089-7096.

Dong LM, Wilson C, Wardell MR, Simmons T, Mahley R, Weisgraber KH, Agard D. Human Apolipoprotein E: Role of arginine 61 in mediating the lipoprotein preferences of the E3 and E4 isoforms. J Biol Chem 1994;269: 22358-22365

Iron A, Richard P, Beucler I, Thomas G, Pascual de Zulueta M, Bereziat G, Cassaigne A, De Gennes JL. Pathology of the human apolipoprotein E gene. Bull Acad Natl Med 1994;178: 415-426

Rall Jr SC, Newhouse YM, Clarke HR, Weisgraber KH, McCarthy BJ, Mahley RW, Bersot TP. Type III hyperlipoproteinemia associated with apolipoprotein E phenotype E3/3. Structure and genetics of an apolipoprotein E3 variant. J Clin Invest.1989; 83:1095-1101.

Rall Jr SC, Weisgraber KH, Innerarity TL, Bersot TP, Mahley RW, Blum CB. Identification of a new structural variant of human apolipoprotein E, E2(Lys146 leads to Gln), in a type III hyperlipoproteinemic subject with the E3/2 phenotype. J Clin Invest 1983;72: 1288-1297.

De Knnijff P, Jjhansen L, Rosseneu M, Frants RR, Jespersen J, Havekes LM. Lipoprotein profile of a Greenland Inuit population. Influcence of and antrophometric variables, ApoE and A4 polymorphism, and lifestyle. Arterioscl Thromb 1992;12: 1371-1379

Dergunov A, Novoselov A, Visvikis S, Siest G, Yakushkin V, Tsibulsky V. The composition, structural properties and binding of very low density and low density lipoproteins to the ldl receptor in normal and hypertriglyceridemia: relation to the apolipoprotein E phenotype. Biol Chem 2005;386: 441-452

Bennouar N, Allami A, Laraqui A, Azeddoug H, El-Kadiri N, Benkouka F, Bendriss A, Ghannam R, Benomar A, Fellat S, Benomar M. Apolipoprotein E and angiotensin-converting enzyme gene polymorphisms as risk factors of coronary disease. Ann Biol Clin 2004;62: 295-304.

Hirashiki A, Yamada Y, Murase Y, Suzuki Y, Kataoka H, Morimoto Y, Tajika T, Murohara T, Yokota M. Association of gene polymorphisms with coronary artery disease in low- or high-risk subjects defined by conventional risk factors. J Am Coll Cardiol 2003; 42: 1429-1437

Mahaley RW. Lipoprotein receptor and cholesterol homeostasis. Biochem Biophys 1983;737: 197-227

Mahaley RW, Angelyn B. Type III hiperlipoproteinemia recent insights into the genetic defect of familial dysbetalipoproteinemia. Adv Intern Med 1984;29: 385-411

Hiroyuki S, Padmaja D, Faye B, Karl H, Weisgraber M, Phillips C, Sissel L-K. Effects of Polymorphism on the Lipid Interaction of Human Apolipoprotein E*. J Biol Chem 2003;278: 40723-40729,

De Andrade M, Thandi I, Brown S, et.al. Relationship of the apolipoprotein E polymorphism with carotid artery atherosclerosis. Am J Hum Genet 1995;56: 1379-1390

Assman G, Schmitz G, Menzel HJ. Apolipoprotein E polymorphism and hyperlipidemia. Clini Chem 1984; 30: 641-643

Kataoka S, Robbins DC, Cowan LD. Apolipoprotein E polymorphism in American Indians and its relation to plasma lipoproteins and diabetes: the Strong Heart Study. Arterioscler Thromb Vasc Biol 1996;16: 918-925

Hanis CL, Hewett-Emmett D, Douglas TC, et.al. Effects of the apolipoprotein E polymorphism on levels of lipids, lipoproteins, and apolipoproteins among Mexican-Americans in Starr County, Texas. Arterioscler Thromb 1991;11: 362-370

Kamboh MI, Sepehnia B, Ferrell RE. Common polymorphism of apolipoprotein E in blacks. Dis Markers 1989;7: 49-55

Luc G, Bard JM, Arveiler D. Impact of apolipoprotein E polymorphism on lipoproteins and risk of myocardial infarction:the ECTIM Study. Arterioscler Thromb 1994;14: 1412-1419

Howard BV, Gidding SS, Lui K. Association of apolipoprotein E phenotype with plasma lipoproteins in African-American and white young adults: the CARDIA Study. Coronary Artery Risk Development in Young Adults. Am J Epidemiol 1998;148: 859-868.

Schaefer EJ, Lamon-Fava S, Johnson S. Effects of gender and menopausal status on the association of apolipoprotein E phenotype with plasma lipoprotein levels: results from the Framingham Offspring Study. Arterioscler Thromb Vasc Biol 1994;14: 1105-1113

Lehtimäki T, Moilanen T, Viikari J. Apolipoprotein E phenotypes in Finnish youths: a cross-sectional and 6-year follow-up study. J Lipid Res 1990;31: 487-495

Mahley RW, Rall Jr SC. Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet 2000;1: 587-593

Eichner JE, Dunn ST, Perveen G, Thompson DM, Stewart KE, Stroehla BC. Apolipoprotein E Polymorphism and Cardiovascular Disease: A HuGE Review. Am J Epidem 2002;155: 487-495

Sorli JV, Velert R, Guillen M, Portoles O, Ramirez JB, Iborra J, Corella D. Effect of the apolipoprotein E poly morphims on lipid levels and cardiovascular diseases risk in a Mediterranean population. Med Clin 2002;118: 569-574

Corbo RM, Scacchi R, Vilardo T, Ruggeri M. Polymorphisms in the Apolipoprotein E gene regulatory region in relation to coronary heart disease and their effect on plasma Apolipoprotein E. Clin Chem Lab Med 2001;39: 2-6

Stengard JH, Weiss KM, Sing CF. An ecological study of association between coronary heart disease mortality rates in men and the relative frequencies of common allelic variations in the gene coding for apolipoprotein E. Hum Genet 1998;103: 234-441.

Staprans I, Pan X, Rapp J, Feingold K. The role of dietary oxidized cholesterol and oxidized fatty acids in the devolopment of atheroslcerosis. Mol Nutr Food Res 2005; 49: 1075-1082

Paduraru I, Hurjui J, Filimon O, Saramet A, Petris O, Lionte C. Recent data about the LDL-atherogenesis relationship. Rev Med Chir Soc Med Nat Iasi 2001;105: 31-6

Reiner Z, Tedeschi-Reiner E. New information on the pathophysiology of atherosclerosis. Lijec Vjesn 2002;123: 26-31

Parthasarathy S, Quinn MT, Steinberg D. Is oxidized low density lipoprotein involved in the recruitment and retention of monocyte/macrophages in the artery wall during the initiation of atherosclerosis. Basic Life Sci 1988; 49: 375-380

Stary H, Chandler A, Dinsmore R, Fuster V, Glagov S, Insull W, Rosenfeld M, CJ. S, Wagner W, Wissler R. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A Report from the Committee on Vascular Lesions of the Council on Atheroslcerosis, American Heart Association. Arterioscler Thromb Vasc Biol 1995; 19: 1512-1531

Wilson PWF, Myers RH, Larson MG. Apo E alleles, dyslipidemia, and coronary heart disease: Tha Framingham Offspring Study. Jama 1994;272:166-171

Hixson JE. Apo E polymorphism effect atherosclerosis in young males. Arterioscl Thromb 1991; 11: 1237-1244.

Lenzen HJ, Assman G, Buchwalsky R, Schulte H. Association of Apo E polymorphism, LDL, and CAD. Clin Chem 1986;32: 778-781

Kuusi T, Nieminen MS, Ehnholm C. Apo E polymorphismand coronary artery diseases: increased prevalencia of E4 in angiographically verified coronary patients. Arteriosclerosis 1989;9: 237-241

Van Bockxmeer FM, Mamotte CD. Apolipoprotein E4 homozygosity in young men with coronary artery disease. Lancet 1992; 340: 879-880

Hertz R, Bishara-SHieban J, Bar-Tana J. Modo of action peroxisome proliferators as hypolipidemic drug, supression of apo C-III. J Biol Chem 1995; 270: 13470-13475

Scuteri A, Najjar SS, Muller D, Andres R, Morrell CH, Zonderman BA, Lakatta EG. ApoE4 allelle and the natural history of cardiovascular risck factors. JAMA 2005;293: 2892-2899

Batalla M. Apolipoprotein E genotype and coronary heart disease. J Am Coll Card 2001;37: 329-330

Utermann G, Langenbeck U, Beisiegel U, Weber W. Genetics of the apolipoprotein E system in man. Am J Hum Genet 1980;32: 339-347.

Lund-Kats S, Wehrli S, Zaiou M, Newhouse Y, Weisgraber KH, Phillips MC. Effect of polymorphims onthe miroenvironment of the LDL receptor-binding region of human apo E. J Lipid Res 2001;42: 894-901

Brewer Jr HB, Gregg RE, Hoeg JM, et.al. Apolipoproteins and lipoproteins in human plasma. Clin Chem 1988;34: 4-8

Zaiou M, Kay A, Newhouse YM, Innerarity R, H WK, Segall M, Phillips C, Sissel L-K. Apolipoprotein E low density lipoprotein receptor interaction: influcences of basic residue and amphipathic alfa helix organization in the ligand. J Lipid Res 2000;41: 1087-1095

Visitas a la página del resumen del artículo

716

Descargas

Los datos de descarga aún no están disponibles.

Cómo citar

Apolipoproteína E y enfermedad cardiovascular. (2006). Revista De La Facultad De Medicina, 54(1), 53-65. https://revistas.unal.edu.co/index.php/revfacmed/article/view/23098