Article information
Fundamento
La paraoxonasa (PON1) es una éster hidrolasa relacionada con la eliminación de componentes oxidados de las lipoproteínas de baja densidad (LDL). El presente estudio analiza la relación entre el título de anticuerpos contra la LDL oxidada (Ac-LDLox), la actividad PON1 en suero y sus polimorfismos genéticos en 39 individuos normales y 39 pacientes supervivientes de un infarto de miocardio
Pacientes y métodosLos valores de Ac-LDLox se determinaron por enzimoinmunoanálisis. La actividad PON1 en suero se determinó mediante la hidrólisis de paraoxon. Los polimorfismos de la PON1 en las posiciones 55 y 192 se analizaron mediante amplificación por reacción en cadena de la polimerasa y análisis de restricción
ResultadosLos resultados obtenidos no demostraron ninguna relación significativa entre los valores de Ac-LDLox ni con la actividad PON1 en suero ni con sus polimorfismos, en sujetos controles o en pacientes con infarto de miocardio
Palabras clave:
Infarto de miocardio
LDL oxidada
Paraoxonasa
Polimorfismos genéticos
Background
Paraoxonase (PON1) is an ester hydrolase related to the elimination of oxidized compounds of LDL particles. The aim of the present study was to analyze the relationship between the antibody titre against oxidized LDL (Ac-LDLox), PON1 activity in serum and its genetic polymorphisms in 39 normal subjects and 39 survivor patients of a myocardial infarction
Patients and methodsAc-LDLox levels were determined by enzymoimmunoassay. PON1 activity was measured by the hydrolysis of paraoxon. PON1 polymorphisms at positions 55 and 192 were analyzed by polymerase chain reaction and restriction isotyping
ResultsResults obtained did not show any significant relationship between Ac-LDLox levels neither with PON1 activity in serum nor with its polymorphisms, in control subjects or in patients with myocardial infarction
Key words:
Myocardial infarction
Oxidized LDL
Paraoxonase
Genetic polymorphisms
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Bibliografía
[1.]
A. Mertens, P. Holvet.
Oxidized LDL and HDL: antagonists in atherothrombosis.
Faseb J, 15 (2001), pp. 2073-2084
[2.]
L. Cominacini, U. Garbin, A.F. Pasini, A. Dvoli, M. Campagnola, G.B. Contessi, et al.
Antioxidants inhibit the expression of intercellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 induced by oxidized LDL on human umbilical vein endothelial cells.
Free Rad Biol Med, 22 (1997), pp. 117-127
[3.]
A. Stiko-Rahm, A. Hultgardh-Nilsson, J. Rengstrom, A. Hamsten, J. Nilsson.
Native and oxidized LDL enhance the production of PDGF and the surface expression of PDGF receptors in cultured smooth muscle cells.
Arterioscler Thromb, 12 (1992), pp. 1099-1109
[4.]
M. Kohno, K. Yokokawa, K. Yasunari, M. Minami, H. Kano, T. Hanehira, et al.
Induction by lysophosphatidylcholine, a major phospholipid component of atherogenic lipoproteins, of human coronary artery smooth muscle cell migration.
Circulation, 98 (1998), pp. 353-359
[5.]
J.K. Liao, W.S. Shin, W.Y. Lee, S.L. Clark.
Oxidized low-density lipoprotein decreases the expression of endothelial nitric oxide synthase.
J Biol Chem, 270 (1995), pp. 319-324
[6.]
F. Vidal, C. Colome, J. Martínez-González, L. Badimon.
Atherogenic concentrations of native low-density lipoproteins down-regulate nitric-oxide-synthase mRNA and protein levels in endothelial cells.
Eur J Biochem, 252 (1998), pp. 378-384
[7.]
K. Heermeier, W. Leicht, A. Palmetshofer, M. Ullrich, C. Wanner, J. Galle.
Oxidized LDL suppresses NF-kappaB and overcomes protection from apoptosis in activated endothelial cells.
J Am Soc Nephrol, 12 (2001), pp. 456-463
[8.]
B. Metzler, Y. Hu, H. Dietrich, Q. Xu.
Increased expression and activation of stress-activated protein kinases/c-Jun NH(2)-terminal protein kinases in atherosclerotic lesions coincide with p53.
Am J Pathol, 156 (2000), pp. 1875-1886
[9.]
L.X. Li, J.X. Chem, D.F. Liao, L. Yu.
Probucol inhibits oxidized-low density lipoprotein-induced adhesion of monocites to endothelial cells by reducing P-selectin synthesis in vitro.
Endothelium, 6 (1998), pp. 1-8
[10.]
D.A. Armstrong.
Oxidized LDL ceroid, and prostaglandin metabolism in human atherosclerosis.
Med Hypotheses, 38 (1992), pp. 244-248
[11.]
M. Navab, S. Hama-Levy, B.J. Van Lenten, G.C. Fonarow, C.J. Cardinez, L.W. Castellani, et al.
Midly oxidized LDL induces an increased apolipoprotein J/paraoxonase ratio.
J Clin Invest, 99 (1997), pp. 2005-2019
[12.]
M. Aviram, M. Rosenblat, S. Billecke, J. Erogul, R. Sorenson, C.L. Bisgaier, et al.
Human serum paraoxonase (PON1) is inactivated by oxidized low density lipoprotein and preserved by antioxidants.
Free Rad Biol Med, 26 (1999), pp. 892-904
[13.]
M. Aviram, E. Hardak, J. Vaya, S. Mahmood, S. Milo, A. Hoffman, et al.
Human serum paraoxonases (PON1) Q and R selectively decrease lipid peroxides in human coronary and carotid atherosclerotic lesions.
Circulation, 101 (2000), pp. 2510-2517
[14.]
B. Mackness, P.N. Durrington, M. Mackness.
Polymorphisms of paraoxonase genes and low-density lipoprotein lipid peroxidation.
Lancet, 353 (1999), pp. 468-469
[15.]
H. Cao, A. Girard-Globa, F. Berthezene, P. Moulin.
Paraoxonase protection of LDL against peroxidation is independent of its esterase activity towards paraoxon and is unaffected by the Q-R genetic polymorphism.
J Lipid Res, 40 (1999), pp. 133-139
[16.]
A. Festa, H.P. Kopp, G. Schernthaner, E.J. Menzel.
Autoantibodies to oxidised low density lipoproteins in IDDM are inversely related to metabolic control and microvascular complications.
Diabetologia, 41 (1998), pp. 350-356
[17.]
T.J. Orchard, G. Virella, K.Y.Z. Forrest, R.W. Evans, D.J. Becker, M.F. Lopes-Virella.
Antibodies to oxidized LDL predict coronary artery disease in type 1 diabetes.
Diabetes, 48 (1999), pp. 1454-1458
[18.]
J. Joven, J.M. Simó, E. Vilella, J. Camps, L. Masana, G. de Febrer, et al.
Lipoprotein(a) and the significance of the association between platelet glycoprotein IIIa polymorphisms and the risk of premature myocardial infarction.
Atherosclerosis, 140 (1998), pp. 155-159
[19.]
N. Ferre, J. Camps, E. Prats, E. Vilella, A. Paul, L. Figuera, et al.
Serum paraoxonase activity: a new additional test for the improved evaluation of chronic liver damage.
Clin Chem, 48 (2002), pp. 261-268
[20.]
B. Halliwell.
Free radicals, antioxidants, and human disease.
Lancet, 344 (1994), pp. 721-724
[21.]
R. Humbert, D.A. Adler, C.M. Disteche, C. Hasset, C.J. Omiecinski, C.E. Furlong.
The molecular basis of the human serum paraoxonase activity polymorphism.
Nature Genet, 3 (1993), pp. 73-76
[22.]
S. Adkins, K.N. Gan, M. Mody, B.N. La Du.
Molecular basis of the polymorphic forms of human serum paraoxonase/arylesterase: glutamine or arginine at position 191, for the respectve A or B allozymes.
Am J Hum Genet, 52 (1993), pp. 598-608
[23.]
D.N. Nevin, A. Zambon, C.E. Furlong, R.J. Richter, R. Humbert, J.E. Hokanson, et al.
Paraoxonase genotypes, lipoprotein lipase activity, and HDL.
Arterioscler Thromb Vasc Biol, 16 (1996), pp. 1243-1249
[24.]
M.C. Blatter Garin, R.W. James, P. Dussoix, H. Blanche, P. Passa, P. Froguel, et al.
Paraoxonase polymorphism Met-Leu 54 is associated with modified serum concentrations of the enzyme. A possible link between the paraoxonase gene and increased cardiovascular risk in diabetes.
J Clin Invest, 99 (1997), pp. 62-66
[25.]
J. Ruiz, H. Blanche, R.W. James, M.C.S. Garin, C. Vaisse, G. Charpentier, et al.
Gln-Arg 192 polymorphism of paraoxonase and coronary heart disease in type 2 diabetes.
Lancet, 346 (1995), pp. 869-872
[26.]
S. Serrato, A.J. Marian.
A variant of human paraoxonase/arylesterase (HUMPONA) gene is a risk factor for coronary heart disease.
J Clin Invest, 96 (1995), pp. 3005-3008
[27.]
D.K. Sanghera, N. Saha, C.E. Aston, M.I. Kamboh.
Genetic polymorphism of paraoxonase and the risk of coronary heart disease.
Arterioscler Thromb Vasc Biol, 17 (1997), pp. 1067-1073
[28.]
M. Odawara, Y. Tachi, K. Yamashita.
Paraoxonase polymorphism (Gln 192-Arg) is associated with coronary heart disease in Japanese non-insulin-dependent diabetes mellitus.
J Clin Endocrinol Metab, 82 (1997), pp. 2257-2260
[29.]
M. Aviram, S. Billecke, R. Sorenson, C. Bisgaier, R. Newton, M. Rosenblat, et al.
Paraoxonase active site required for protection against LDL oxidation involves its free sulfhydryl group and is different that required for its arylesterase/paraoxonase activities: selective action of human paraoxonase allozymes Q and R.
Arterioscler Thromb Vasc Biol, 18 (1998), pp. 1617-1625
[30.]
M.I. Mackness, S. Arrol, B. Mackness, P.N. Durrington.
Alloenzymes of paraoxonase and the effectiveness of high-density lipoprotein in protecting low-density lipoprotein against lipid peroxidation.
Lancet, 349 (1997), pp. 851-852
[31.]
B. Mackness, P.N. Durrington, M.I. Mackness.
Polymorphisms of paraoxonase genes and low-density lipoprotein lipid peroxidation.
Lancet, 353 (1999), pp. 468-469
[32.]
M.I. Aviram, E. Hardak, J. Vaya, S. Mahmood, S. Milo, A. Hoffman, et al.
Human serum paraoxonases (PON1) Q and R selectively decrease lipid peroxides in human coronary and carotid atherosclerotic lesions. PON1 esterase and peroxidase-like activities.
Circulation, 101 (2000), pp. 2510-2517
[33.]
M. Antikainen, S. Murtomaki, M. Syvanne, R. Pahlman, E. Tahvanainen, M. Jauhianen, et al.
The Gln-Arg 191 polymorphism of the human paraoxonase gene (HUMPONA) is not associated with the risk of coronary artery disease in Fins.
J Clin Invest, 98 (1996), pp. 883-885
[34.]
S.M. Herrmann, H. Blanc, O. Poirier, D. Arveiler, G. Luc, A. Evens, et al.
The Gln/Arg polymorphism of human paraoxonase (PON192) is not related to myocardial infarction in the ECTIM study.
Atherosclerosis, 126 (1996), pp. 299-303
[35.]
T. Suehiro, Y. Nakauchi, M. Yamamoto, K. Arii, H. Itoh, N. Hammashige, et al.
Paraoxonase gene polymorphism in Japanese subjects with coronary heart diseae.
Int J Cardiol, 57 (1996), pp. 69-73
[36.]
Ferré N, Tous M, Paul A, Zamora A, Vendrell JJ, Bardají A, et al. Paraoxonase Gln-Arg (192) and Leu-Met (55) gene polymorphisms and enzyme activity in a population with a low rate of coronary heart disease [en prensa]. Clin Biochem
[37.]
R. Malin, J. Knuuti, T. Janatuien, R. Laaksonen, R. Vesalainen, P. Nuutila, et al.
Paraoxonase gene polymorphisms and coronary reactivity in young healthy men.
J Mol Med, 79 (2001), pp. 449-458
[38.]
T. Lehtimäki, A. Lehtinen, T. Solakivi, M. Nikkila, O. Jaakkola, H. Jokela, et al.
Autoantibodies against oxidized low density lipoprotein in patients with angiographically verified coronary artery disease.
Arterioscler Thromb Vasc Biol, 19 (1999), pp. 23-27
[39.]
E. Maggi, R. Bellazzi, F. Falaschi, A. Frattoni, G. Perani, G. Finardi, et al.
Enhanced LDL oxidation in uremic patients: an additional mechanism for accelerated atherosclerosis?.
Kidney Int, 45 (1994), pp. 876-883
[40.]
A. Shanti, N. Santanam, A.J. Morales, S. Parthasarathy, A.A. Murphy.
Autoantibodies to markers of oxidative stress are elevated in women with endometriosis.
Fertil Steril, 71 (1999), pp. 1115-1118
[41.]
T.J. Orchard, G. Virella, K.Y. Forrest, R.W. Evans, D.J. Becker, M.F. Lopes-Virella.
Antibodies to oxidized LDL predict coronary artery disease in type diabetes: a nested case-control study from the Pittsburg Epidemiology of Diabetes Complications Study.
Diabetes, 48 (1999), pp. 1454-1458
[42.]
C. Bergmark, R. Wu, U. de Fraire, A.K. Lefvert, J. Swedenborg.
Patients with early-onset peripheral vascular disease have increased levels of autoantibodies against oxidized LDL.
Arterioscler Thromb Vasc Biol, 15 (1995), pp. 441-445
[43.]
M.I. Uusitupa, L. Niskanen, J. Luoma, P. Vilja, M. Mercuri, R. Rauramaa, et al.
Autoantibodies against oxidized LDL do not predict atherosclerotic vascular disease in non-insulin-dependent diabetes mellitus.
Arterioscler Thromb Vasc Biol, 16 (1965), pp. 1236-1242
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