2004, Número 1
<< Anterior Siguiente >>
Arch Cardiol Mex 2004; 74 (1)
Lipoproteínas de alta densidad (HDL). ¿Un objetivo terapéutico en la prevención de la aterosclerosis?
Pérez-Méndez O
Idioma: Español
Referencias bibliográficas: 60
Paginas: 53-67
Archivo PDF: 183.56 Kb.
RESUMEN
Las lipoproteínas de alta densidad (HDL) son una familia de partículas que difieren en tamaño, densidad y composición química. La heterogeneidad de las HDL resulta de la velocidad de síntesis y de catabolismo de las partículas, y de la acción de enzimas y proteínas de transporte que las remodelan continuamente. Los bajos niveles de colesterol HDL correlacionan con un riesgo elevado de desarrollar enfermedad aterosclerosa coronaria. La disminución de las HDL afecta el transporte reverso de colesterol, que es la vía metabólica responsable de la remoción del colesterol excedente de la células periféricas y su transporte hacia el hígado para reciclarlo o eliminarlo. Las HDL poseen además propiedades antiinflamatorias, antioxidativas, antiagregatorias, anticoagulantes y profibrinolíticas in vitro. Algunas de estas propiedades potencialmente antiaterosclerosas, también se han puesto de manifiesto in vivo con infusiones de HDL. Estas evidencias, además de la protección que se logra en modelos animales genéticamente modificados, permite plantear a las HDL como un objetivo primario en la prevención de la aterosclerosis coronaria. Algunos estudios epidemiológicos han demostrado una reducción importante en el riesgo cardiovascular asociado a elevaciones del colesterol HDL, principalmente en prevención secundaria. En consecuencia, elevar las concentraciones de las HDL a través de medidas higiénicas como el ejercicio aeróbico, la pérdida de peso y eliminar el tabaquismo, es ampliamente recomendado para reducir el riesgo coronario. Cuando las medidas higiénicas fallan, la intervención farmacológica con niacina o fibratos debe ser considerada en ciertos pacientes con niveles bajos de HDL. Por último, las diferentes subclases de HDL no poseen las mismas propiedades antiaterogénicas, lo que sugiere que las intervenciones tanto higiénicas como farmacológicas se deberán enfocar en el futuro hacia incrementos de la funcionalidad de las HDL, más que a incremento en la concentración del colesterol HDL.
REFERENCIAS (EN ESTE ARTÍCULO)
Yamashita S, Maruyama T, Hirano KI, Sakai N, Nakajima N, Matsuzawa Y: Molecular mechanisms, lipoprotein abnormalities and atherogenicity of hyperalphalipoproteinemia. Atherosclerosis 2000; 152: 271-285.
Barter PJ, Brewer HB, Chapman MJ, Hennekens CH, Rader DJ, Tall AR: Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis. Arterioscler Thromb Vasc Biol 2003; 23: 160-167.
Huesca-Gómez C, Franco M, Luc G, Montaño LF, Masso F, Posadas-Romero C, Pérez-Méndez O: Chronic hypothyroidism induces abnormal structure of high-density lipoproteins and impaired kinetics of apolipoprotein A-I in the rat. Metabolism 2002; 51: 443-450.
Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001; 285: 2486-2497.
Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002; 106: 3143-3421.
Moss AJ, Goldstein RE, Marder VJ, Sparks CE, Oakes D, Greenberg H, et al: Thrombogenic factors and recurrent coronary events. Circulation 1999; 99: 2517-2522.
Wilson PW, Garrison RJ, Castelli WP, Feinleib M, McNamara PM, Kannel WB: Prevalence of coronary heart disease in the Framingham Offspring Study: role of lipoprotein cholesterols. Am J Cardiol 1980; 46: 649-654.
Assmann G, Schulte H, von Eckardstein A, Huang Y: High-density lipoprotein cholesterol as a predictor of coronary heart disease risk: the PROCAM experience and pathophysiological implications for reverse cholesterol transport. Atherosclerosis 1996; 124: S11-S20.
Schaefer EJ, Lamon-Fava S, Ordovas JM, Cohn SD, Schaefer MM, Castelli WP, Wilson PWF: Factors associated with low and elevated plasma high-density lipoprotein cholesterol and apolipoprotein A-I levels in the Framingham Offspring Study. J Lipid Res 1994; 35: 871-882.
Wilson PWF, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB: Prediction of coronary heart disease using risk factor categories. Circulation 1998; 97:1837-1847.
Elkhalil L, Majd Z, Bakir R, Pérez-Méndez O, Castro G, Poulain P, et al: Fish-eye disease: structural and in vivo metabolic abnormalities of high-density lipoproteins. Metabolism 1997; 46: 474-483.
Pérez-Méndez O, Bruckert E, Franceschini G, Duhal N, Lacroix B, Bonte JP, et al: Metabolism of apolipoproteins AI and AII in subjects carrying similar apoAI mutations, apoAI Milano and apoAI Paris. Atherosclerosis 1999; 148: 317-325.
Pérez-Méndez O, Luc G, Posadas-Romero C: Concentraciones bajas de lipoproteínas de alta densidad (HDL) en plasma y enfermedad arterial coronaria. Arch Inst Cardiol Méx 2000; 70: 312-321.
Brooks-Wilson A, Marcil M, Clee SM, Zhang LH, Roomp K, van Dam M, et al: Mutations in ABC1 in Tangier disease and familial high-density lipoprotein deficiency. Nat Genet 1999; 22: 336-345.
Clee SM, Kastelein JJ, van Dam M, Marcil M, Roomp K, Zwarts KY, et al: Age and residual cholesterol efflux affect HDL cholesterol levels and coronary artery disease in ABCA1 heterozygotes. J Clin Invest 2000; 106: 1263–1270.
Singaraja RR, Bocher V, James ER, Clee SM, Zhang LH, Leavitt BR, et al: Human ABCA1 BAC transgenic mice show increased HDL-C and ApoAI dependent efflux stimulated by an internal promoter containing LXREs in intron 1. J Biol Chem 2001; 276: 33969-33979.
Aviram M, Rosenblat M, Bisgaier CL, Newton RS, Primo-Parmo SL, LaDu B: Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase. J Clin Invest 1998; 101: 1581-1590.
Ruiz J, Blanche H, James RW, Garin MC, Vaisse C, Charpentier G, et al: Gln-Arg192 polymorphism of paraoxonase and coronary heart disease in type 2 diabetes. Lancet 1995; 346: 869-872.
Serrato M, Marian AJ: A variant of human paraoxonase/arylesterase (HUMPONA) gene is a risk factor for coronary artery disease. J Clin Invest 1995; 96: 3005-3008.
Odawara M, Tachi Y, Yamashita K: Paraoxonase polymorphism (Gln192-Arg) is associated with coronary heart disease in Japanese noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1997; 82: 2257-2260.
Anurag P, Anuradha CV: Metformin improves lipid metabolism and attenuates lipid peroxidation in high fructose-fed rats. Diabetes Obes Metab 2002; 4: 36-42.
James RW, Blatter GM, Calabresi L, Miccoli R, von Ekardstein A, Tilly-Kiesi M, et al: Modulated serum activities and concentrations of paraoxonase in high-density lipoprotein deficiency states. Atherosclerosis 1998; 139: 77-82.
Hedrick CC, Thorpe SR, Fu MX, Harper CM, Yoo J, Kim SM, et al: Glycation impairs high-density lipoprotein function. Diabetologia 2000; 43: 312-320.
Cascorbi I, Laule M, Mrozikiewicz PM, Mrozikiewicz A, Andel C, Baumann G, et al: Mutations in the human paraoxonase 1 gene: frequencies, allelic linkages, and association with coronary artery disease. Pharmacogenetics 1999; 9: 755-761.
Castellani LW, Navab M, Lenten BJV, Hedrick CC, Hama SY, Goto AM, et al: Overexpression of apolipoprotein AII in transgenic mice converts high density lipoproteins to proinflammatory particles. J Clin Invest 1997; 100: 464-474
Deakin S, Leviev I, Gomaraschi M, Calabresi L, Franceschini G, James RW: Enzymatically active paraoxonase-1 is located at the external membrane of producing cells and released by a high affinity, saturable, desorption mechanism. J Biol Chem 2002; 277: 4301-4308.
Zhang X, Zhao SP, Li XP, Gao M, Zhou QC: Endothelium-dependent and -independent functions are impaired in patients with coronary heart disease. Atherosclerosis 2000; 149: 19-24.
Li XP, Zhao SP, Zhang XY, Liu L, Gao M, Zhou QC: Protective effect of high-density lipoprotein on endothelium-dependent vasodilatation. Int J Cardiol 2000; 73: 231-236.
Kaufmann PA, Gnecchi-Ruscone T, Schafers KP, Luscher TF, Camici PG: Low-density lipoprotein cholesterol and coronary microvascular dysfunction in hypercholesterolemia. J Am Coll Cardiol 2000; 36: 103-109.
Cockerill GW, Rye KA, Gamble JR, Vadas MA, Barter PJ: High-density lipoproteins inhibit cytokine-induced expression of endothelial cell adhesion molecules. Arterioscler Thromb Vasc Biol 1995; 15: 1987-1994.
Calabresi L, Franceschini G, Sirtori CR, De PA, Saresella M, Ferrante P, Taramelli D: Inhibition of VCAM-1 expression in endothelial cells by reconstituted high-density lipoproteins. Biochem Biophys Res Commun 1997; 238: 61-65.
Kaneko T, Wada H, Wakita Y, Minamikawa K, Nakase T, Mori Y, et al: Enhanced tissue factor activity and plasminogen activator inhibitor-1 antigen in human umbilical vein endothelial cells incubated with lipoproteins: Blood Coagul Fibrinolysis 1994; 5: 385-392.
Rubin EM, Krauss R, Spangler E, Verstuyft S, Clift S: Inhibition of early atherogenesis in transgenic mice by human apolipoprotein A-I. Nature 1991; 353: 265-267.
Nanjee MN, Dora JE, Lerch PG, Miller NE: 1999: Acute effects of intravenous infusion of apo A-I/phosphatidylcholine discs on plasma lipoproteins in humans. Arterioscler Thromb Vasc Biol 1999; 19: 979-989
Eriksson M, Carlson LA, Miettinen TA, Angelin B: Stimulation of fecal steroid excretion after infusion of recombinant proapolipoprotein A-I. Potential reverse cholesterol transport in humans. Circulation 1999; 100: 594-598.
Spieker LE, Sudano I, Hurlimann D, Lerch PG, Lang MG, Binggeli C, et al: High-density lipoprotein restores endothelial function in hypercholesterolemic men. Circulation 2002; 105: 1399-1402.
Bisoendial RJ, Hovingh GK, Levels JH, Lerch PG, Andresen I, Hayden MR, et al: Restoration of endothelial function by increasing high-density lipoprotein in subjects with isolated low high-density lipoprotein. Circulation 2003; 107: 2944-2948.
Shah PK, Yano J, Reyes O, Chyu KY, Kaul S, Bisgaier CL, et al: High-dose recombinant apolipoprotein A-I(milano) mobilizes tissue cholesterol and rapidly reduces plaque lipid and macrophage content in apolipoprotein e-deficient mice. Potential implications for acute plaque stabilization. Circulation 2001; 103: 3047-3050.
Kaul S, Rukshin V, Santos R, Azarbal B, Bisgaier CL, Johansson J, et al: Intramural delivery of recombinant apolipoprotein A-IMilano/phospholipid complex (ETC-216) inhibits in-stent stenosis in porcine coronary arteries. Circulation 2003; 107: 2551-2554
Cole TG, Nowatzke WL, Bisgaier CL, Krause BR: Method-dependent changes in ‘HDL-Cholesterol’ with recombinant apolipoprotein A-I Milano infusion in healthy volunteers. Clin Chem 2002; 48: 680-681.
Rodrigueza WV, Mazany KD, Essenburg AD, Pape ME, Rea TJ, Bisgaier CL, Williams KJ: Large versus small unilamellar vesicles mediate reverse cholesterol transport in vivo into two distinct hepatic metabolic pools. Implications for the treatment of atherosclerosis. Arterioscler Thromb Vasc Biol 1997; 17: 2132-2139.
Williams KJ, Scalia R, Mazany KD, Rodrigueza WV, Lefer AM: Rapid restoration of normal endothelial functions in genetically hyperlipidemic mice by a synthetic mediator of reverse lipid transport. Arterioscler Thromb Vasc Biol 2000; 20: 1033-1039.
Esperion Therapeutics, Inc. News Release. http://www.esperion.com, Julio 15, 2002.
de Grooth GJ, Kuivenhoven JA, Stalenhoef AF, de Graaf J, Zwinderman AH, Posma JL, et al: Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans: a randomized phase II dose-response study. Circulation 2002; 105: 2159-2165.
Foger B, Chase M, Amar MJ, Vaisman BL, Shamburek RD, Paigen B, et al: Cholesteryl ester transfer protein corrects dysfunctional high-density lipoproteins and reduces aortic atherosclerosis in lecithin cholesterol acyltransferase transgenic mice. J Biol Chem 1999; 274: 36912-36920.
Bloomfield RH, Davenport J, Babikian V, Brass LM, Collins D, Wexler L, et al: Reduction in stroke with gemfibrozil in men with coronary heart disease and low HDL cholesterol: The Veterans Affairs HDL Intervention Trial (VA-HIT). Circulation 2001; 103: 2828-2833.
Devroey D, Velkeniers B, Duquet W, Betz W: Serum lipid comparison in patients treated by statins or fibrates: existence of bad HDL-C responders to statins. Acta Cardiol 2003; 58: 179-184.
Martin G, Duez H, Blanquart C, Berezowski V, Poulain P, Fruchart JC, et al: Statin-induced inhibition of the Rho-signaling pathway activates PPARalpha and induces HDL apoA-I. J Clin Invest 2001;107: 1423-1432
Shalev A, Meier CA: The peroxisome proliferator-activated receptor alpha is a phosphoprotein: regulation by insulin. Endocrinology 1996; 137: 4499–4502.
Pérez-Méndez O, Castro G, Fruchart J-C, Luc G: Kinetic and metabolic studies of apo A-I and apo A-II in an hypoalphalipoproteinemic patient. Eur J Neurology 1995, (Suppl 2): 77.
Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, Friedewald W: Fifteen year mortality in coronary drug project patients: long-term benefit with niacin. J Am Coll Cardiol 1986; 8: 1245–1255.
Blankenhorn DH, Nessim SA, Johnson RL, Sanmarco ME, Azen SP, Cashin-Hemphill L: Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts. JAMA 1987; 257: 3233–3240.
Blum CB, Levy RL, Eisenberg S, Hall MIII, Goebel RH, Berman M: High-density lipoprotein metabolism in man. J Clin Invest. 1977; 60: 795–807.
Sakai T, Kamanna S, Kashyap ML: Niacin, but not gemfibrozil, selectively increases LP-AI, a cardioprotective subfraction of HDL, in patients with low HDL-cholesterol. Arterioscler Thromb Vasc Biol 2001; 21: 1783–1789.
Capuzzi DM, Morgan JM, Weiss RJ, Chitra RR, Hutchinson HG, Cressman MD: Beneficial effects of rosuvastatin alone and in combination with extended-release niacin in patients with a combined hyperlipidemia and low high-density lipoprotein cholesterol levels. Am J Cardiol 2003; 91: 1304-1310.
Dattilo AM, Kris-Etherton PM: Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis. Am J Clin Nutr 1992: 56: 320-328.
Moffatt RJ, Biggerstaff KD, Stamford BA: Effects of the transdermal nicotine patch on normalization of HDL-C and its subfractions. Prev Med 2000: 31: 148-152.
Prado ES, Dantas EH: Effects of aerobic and of strength physical exercises on HDL and LDL lipoproteins and lipoprotein(a). Arq Bras Cardiol 2002; 79: 429-433.
Saks FM: The role of high-density lipoprotein (HDL) cholesterol in the prevention and treatment of coronary heart disease: expert group recommendations. Am J Cardiol 2002; 90: 139-142.
Aguilar-Salinas CA, Olaiz G, Valles V, Torres JM, Gomez PF, Rull JA, et al: High prevalence of low HDL cholesterol concentrations and mixed hyperlipidemia in a Mexican nationwide survey. J Lipid Res 2001; 42: 1298-1307.