None

Resúmenes

El término LDL oxidada es utilizado para describir una amplia variedad de preparaciones de LDL que han sido modificadas ex vivo bajo condiciones definidas o aisladas de fuentes biológicas. La oxidación de la partícula de LDL es un proceso complejo en el cual la proteína y los lípidos constituyentes sufren cambios oxidativos originando productos complejos. La LDL oxidada juega un papel clave en la iniciación y la progresión de la aterogénesis caracterizada por una inflamación crónica, la acumulación de lípidos y modificaciones de las células vasculares en la pared arterial. A diferencia de las LDL nativas, las LDL oxidadas no son reconocidas por los receptores de LDL y más bien son captadas en una forma no regulada por receptores scavenger en las células vasculares. Este proceso lleva a la acumulación de colesterol en la pared vascular originando las células espumosas, características de la lesión aterosclerótica. Niveles aumentados de LDL oxidada han sido demostrados en pacientes con enfermedad arterial coronaria (CAD) y sugieren que el nivel plasmático de la LDL oxidada puede ser un marcador de CAD.

Aterosclerosis; colesterol; lipoproteína de baja densidad oxidada

The term “oxidized LDL” is used to describe a wide variety of LDL preparations that have oxidatively modified <span name="style_italic">ex vivo </span>under defined conditions, or isolated from biological sources. The oxidation of LDL is a complex process during which the protein and the lipids undergo oxidative changes and form complex products. Ox-LDL is believed to play a key role in the initiation and progression of atherogenesis characterized by chronic inflammation, accumulation of lipids and vascular cell modifications in the arterial wall. Unlike native LDLs, ox-LDLs are not recognized by the LDL receptors, but are taken up in a non-regulated manner by the scavenger receptors in vascular cells. This process leads to the accumulation of cholesterol in the vascular cells, forming foam cells, the hallmark of the atherosclerosis lesión. Increased levels of oxidized LDL have been demostrated in patients with coronary artery disease and it suggests that the plasma level of oxidized LDL may be a marker of coronary artery disease (CAD).under defined conditions, or isolated from biological sources. The oxidation of LDL is a complex process during which the protein and the lipids undergo oxidative changes and form complex products. Ox-LDL is believed to play a key role in the initiation and progression of atherogenesis characterized by chronic inflammation, accumulation of lipids and vascular cell modifications in the arterial wall. Unlike native LDLs, ox-LDLs are not recognized by the LDL receptors, but are taken up in a non-regulated manner by the scavenger receptors in vascular cells. This process leads to the accumulation of cholesterol in the vascular cells, forming foam cells, the hallmark of the atherosclerosis lesión. Increased levels of oxidized LDL have been demostrated in patients with coronary artery disease and it suggests that the plasma level of oxidized LDL may be a marker of coronary artery disease (CAD).

Atherosclerosis; cholesterol; oxidized low density lipoprotein

Carlos Carvajal Carvajal^*+

Resumen:

The term oxidized LDL is used to describe a wide variety of LDL preparations that have oxidatively modified ex vivo under defined conditions, or isolated from biological sources.

El término LDL oxidada (LDLox) se refiere a una amplia gama de preparaciones de LDL que han sido modificadas ex vivo bajo condiciones definidas, o aisladas de fuentes biológicas y que tienen en común la generación o presencia de una partícula oxidada.

in vitro los productos pueden diferir significativamente, dependiendo de la composición de ácidos grasos y del estado antioxidante de la preparación de LDL original. Debe recordarse que la LDL constituye una población heterogénea con respecto a su composición lipídica y esto resultará también en una producción de LDLox heterogénea.

in vitro y las preparaciones aisladas de tejidos difieren significativamente de laboratorio a laboratorio en su composición y en sus efectos biológicos y por tanto el principal problema de comparar resultados de estudios de LDLox de diferentes laboratorios es la heterogeneidad de las preparaciones empleadas. La composición química detallada de las LDLox utilizadas casi nunca es reportada y ante la gran variedad de LDLox utilizadas la comparación de resultados se vuelve poco confiable.

Origen y composición de las LDLox

in vivo capaces de oxidar a las LDL incluyendo los metales de transición (hierro y cobre), y diferentes sistemas enzimáticos como lipooxigenasas, ceruloplasmina, mieloperoxidasa, NADPH oxidasa y óxido nítrico sintetasa (8-12). Los investigadores Satchell y Leake incluso demostraron que la LDL puede ser oxidada intracelularmente en los lisosomas de los macrófagos(13).

in vivo.

in vivo en la pared arterial y estimula a las células endoteliales a producir moléculas proinflamatorias que reclutan a los monocitos y promueven su diferenciación a macrófagos(6). Westhorpe y colaboradores utilizando monocapas de células endoteliales humanas con una matriz extracelular de base demostraron que la activación de las células endoteliales por LDLox causaba la migración de monocitos a través de la monocapa, su acumulación en la matriz y su transformación en células espumosas por una captación aumentada de LDLox(23).

in vivo como in vitro(38).

in vivo en su estructura y en sus propiedades a partir de la acción de diversas enzimas y cationes metálicos originando la LDL oxidada.

Referencias bibliográficas

1. Bornfeldt, K. & Tabas, I. (2011). Insulin resistance, hyperglycemia and atherosclerosis. Cell Metab, 14, 5, 575-585.
2. Djärv, T., Wilkman, A. & Lagergren, P. (2012). Number and burden of cardiovascular diseases in relation to health-related queality of life in a cross-sectional population- based cohort study. BMJ Open, 2, 1-7.
3. Catapano, A., Reiner, Z., De-Backer, G., Graham, I., Taskinen, M. & Wiklund, O., et al. (2011). ESC/EAS Guidelines for the management of dyslipidaemias the task forcé for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis, 217, 3- 46.
4. Levitan, I., Volkov, S. & Subbaiah, V. (2010). Oxidized LDL: diversity, patterns of recognition, and pathophysiology. Antioxidants y Redox Signaling, 13, 1, 39-74.
5. Estruch, M., Sánchez, J, Ordoñez, J. & Benitez, S. (2013). Electronegative LDL: a circulating modified LDL with a role in inflammation. Mediators of Inflamation, 2013,1-13.
6. Estronca, L., Silva, J., Sampaio, J., Shevchenko, A. & Verkade, P., et al. (2012). Molecular etiology of atherosclerosis-in vitro induction of lipidosis in macrophages with a new LDL model. PLOS ONE, 7, 4, 1-14.
7. Itabe, H., Yamamoto, H., Imanaka, T., Shimamura, K., Uchiyama, H., Kimura, J., et al. (1996). Sensitive detection of oxidatively modified low density lipoprotein using a monoclonal antibody. J. Lipid. Res, 37, 45-53.
8. Tsimikas, S. & Miller, Y. (2011). Oxidative modification of lipoproteins: mechanisms, role in inflammation and potential Clinical applications in cardiovascular disease. Curr. Pharm. Des, 17, 27-37.
9. Delporte, C., Van Antwerpen, P., Vanhamme, L. & Roumeguére, Z. (2013). Low- density lipoprotein modified by mieloperoxidase in inflammatory pathways and Clinical studies. Mediators of Inflammation, 2013, 1-18.
10. Ehrenwald, E. & Fox, P. (1995). Role of endogenous ceruloplasmin in low density lipoprotein oxidation by human U937 monocytic cells. J.Clin. Invest, 97, 3, 884-890.
11. Ehrenwald, E., Chisolm, G. & Fox, P. (1994). Intact human ceruloplasmin oxidatively modifies low density lipoprotein. Biochem. J., 93, 1493-1501.
12. OLeary, V., Darley, V., Rusell, L. & Stone, D. (1992). Pro-oxidant effects of lipoxygenase-derived peroxides on the copper.initiated oxidation of low density lipoprotein. Biochem. J., 282, 631-634.
13. Satchell, L. & Leake, D. (2012). Oxidation of low-density lipoprotein by iron at lysosomal pH: implications for atherosclerosis. Biochemistry, 51, 3767-3775.
14. Parthasarathy, S., Raghavamenon, A., Garelnabi, M. & Santanam, N. (2010). Oxidized low-density lipoprotein. Methods Mol Biol, 610, 403-417.
15. Frostegard, J. (2013). Immunity, atherosclerosis and cardiovascular disease. BMC Medicine, 11, 117-129.
16. Silverstein, R., Li, W., Park, Y. & Raham, O. (2010). Mechanism of cell signaling by the scavenger receptor CD36: implications in atherosclerosis and thrombosis. Transactions of the American Clinical and Climatological Association, 121, 206- 220.
17. Paoletti, R., Gotto, A. & Hajjar, D. (2004). Inflammation in atherosclerosis and implications for therapy. Circulation, 109 (supplIII), III20-III26.
18. Chang, S. H, Johns, M., Boyle, J., McConnell, E., Kirkham, P., Bicknell C., et al. (2012). Model IgG monoclonal autoantibody-anti-idiotype pair for dissecting the humoral immmune response to oxidized low density lipoprotein. Hybridoma, 31, 2, 87-98.
19. Virella, G. & Lopes, M. (2008). Atherogenesis and the humoral response to modified lipoproteins. Atherosclerosis, 200, 2, 239-246.
20. Horkko, S., Bird, D., Miller, E., Itabe, H., Leitinger, N., Subbanagounder, G., Berliner, J., et al. (1999). Monoclonal antibodies specific for oxidized phospholipids or oxidized phospholipid-protein adducts inhibit macrophage uptake of oxidized low- density lipoproteins. The Journal of Clinical Investigation, 103, 1, 117-129.
21. Davignon, J. & Ganz, P. (2004). Role of endothelial dysfunction in atherosclerosis. Circulation, 109 (supplIII), III-27 III-32.
22. Wang, W., Hein, T., Zhang, C., Zawieja, D., Liao, J. & Kuo, L. (2011). Oxidized low- density lipoprotein inhibits oxide-mediated coronary arteriolar dilation by up- regulating endotelial arginase I. Microcirculation, 18, 1, 36-45.
23. Westhorpe, C., Dufour, E., Maisa, A., Jaworowski, A., Crowe, S. & Muller, W. (2012). Endothelial cell activation promotes foam cell formation by monocytes following transendothelial migration in an in vitro model. Exp Mol Pathol, 93, 2, 220-226.
24. Chen, J., Liu, Y., Hermonat, P. & Mehta, J. (2006). Lectin-like oxidized low-density lipoprotein receptor-1 (LOX- 1) transcriptional regulation by Oct-1 in human endotelial cells: implications for atherosclerosis. Biochem. J., 393, 255-265.
25. Dong, Q., Xiang, R., Zhang, D. & Qin, S. (2013). OX-LDL increases OX40L in endotelial cells through a LOX-1 dependent mechanism. Brazilian Journal of Medical and Biological Research, 46, 765-770.
Cardiovasc Drugs, 25, 379-39
27. Huang, Y., Hu, Y., Mai, W., Cai, X., Song, Y., Wu, Y., et al. (2011). Plasma oxidized low- density lipoprotein is an independent risk factor in Young patients with coronary disease. Disease Markers, 31, 295-301.
28.Park, Y., Drazba, J., Vasanji, A., Egelhoff, T., Febbraio, M. & Silverstein, R. (2012). Oxidized LDL/CD36 interaction induces loss of cell polarity and inhibits macrophage locomotion. Molecular Biology of the Cell, 23, 3057-3068.
29. Go, G. W. & Mani, A. (2012). Low-density lipoprotein receptor (LDLR) Family orchestrates cholesterol homeostasis. Yale Journal of Biology and Medicine, 85, 19-28.
30. Ding, Z., Liu, S., Yang, B., Fan, Y. & Deng, X. (2012). Effect of oxidized low-density lipoprotein concentration polarization on human smooth muscle cells, proliferation, cycle, apoptosis and ozidized low-density lipoprotein uptake J. R. Soc. Interface, 9, 1233-1240.
31. Yu, J., Li, Y., Li, M., Qu, Z., & Ruan, Q. (2010). Oxidized low-density lipoprotein- induced transdefferentiation of bone marrow-derived smooth muscle-like cells into foam-like cells in vitro. Int. J. Exp. Path, 91, 24-33.
32. Moore, K. & Tabas, I. (2011). The cellular biology of macrophages in atherosclerosis. Cell, 145, 3, 341-355.
33. Maiolino, G., Rossitto, G., Caielli, P., Bisogni, V., Rossi, G. & Caló, L. (2013). The role of oxidized lo-density lipoproteins in atherosclerosis: the myths and the facts. Mediators of Inflammation, 2013, 1-13.
34. Asgary, S., Saberi, S. A. & Azampanah, S. (2007). Effect of immunization against ox- LDL with two different antgens on formation and Development of atherosclerosis. BioMed, 6,1, 32-37.
35. Huang, H., Mai, W., Liu, D., Hao, Y., Tao, J. & Dong, Y. (2008). The oxidation ratio of LDL: a predictor for coronary artery disease. Disease Markers, 24, 341-349.
36. Aoki, T., Abe, T., Yamada, E., Matsuto, T. & Okada, M. (2012). Increased LDL susceptibility to oxidation accelerates future carotid srtery atherosclerosis. Lipids in Health an Disease,11, 4-10.
37. Zuliani, G., Morieri, M., Volpato, S., Vigna, G., Bosi, C., Maggio, M., et al. (2013). Determinants and clinical significance of plasma oxidized LDLs in older individuals. A years follow-up study. Atherosclerosis, 226, 1, 201-207.
38. Dong, Y., Zhang, M., Wang, S., Liang, B., Zhao, Z., Liu, C., et al. (2010). Activation of AMP-activated Protein Kinase inhibits oxidized LDL-triggered endoplasmic reticulum stress in vivo. Diabetes, 59, 1386-1396.

^* Microbiólogo Especialista en Química Clínica. Laboratorio Clínico, Hospital de Guápiles.

Recibido para publicación el 20 de noviembre de 2014 Aceptado el 10 de diciembre de 2014

Fechas de Publicación

Publicación en esta colección
29 Mayo 2015
Fecha del número
Mar 2015

Histórico

Recibido
20 Nov 2014
Acepto
10 Dic 2014

[1] 1. Bornfeldt, K. & Tabas, I. (2011). Insulin resistance, hyperglycemia and atherosclerosis. Cell Metab, 14, 5, 575-585.

[2] 2. Djärv, T., Wilkman, A. & Lagergren, P. (2012). Number and burden of cardiovascular diseases in relation to health-related queality of life in a cross-sectional population- based cohort study. BMJ Open, 2, 1-7.

[3] 3. Catapano, A., Reiner, Z., De-Backer, G., Graham, I., Taskinen, M. & Wiklund, O., et al. (2011). ESC/EAS Guidelines for the management of dyslipidaemias the task forcé for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Atherosclerosis, 217, 3- 46.

[4] 4. Levitan, I., Volkov, S. & Subbaiah, V. (2010). Oxidized LDL: diversity, patterns of recognition, and pathophysiology. Antioxidants y Redox Signaling, 13, 1, 39-74.

[5] 5. Estruch, M., Sánchez, J, Ordoñez, J. & Benitez, S. (2013). Electronegative LDL: a circulating modified LDL with a role in inflammation. Mediators of Inflamation, 2013,1-13.

[6] 6. Estronca, L., Silva, J., Sampaio, J., Shevchenko, A. & Verkade, P., et al. (2012). Molecular etiology of atherosclerosis-in vitro induction of lipidosis in macrophages with a new LDL model. PLOS ONE, 7, 4, 1-14.

[7] 7. Itabe, H., Yamamoto, H., Imanaka, T., Shimamura, K., Uchiyama, H., Kimura, J., et al. (1996). Sensitive detection of oxidatively modified low density lipoprotein using a monoclonal antibody. J. Lipid. Res, 37, 45-53.

[8] 8. Tsimikas, S. & Miller, Y. (2011). Oxidative modification of lipoproteins: mechanisms, role in inflammation and potential Clinical applications in cardiovascular disease. Curr. Pharm. Des, 17, 27-37.

[9] 9. Delporte, C., Van Antwerpen, P., Vanhamme, L. & Roumeguére, Z. (2013). Low- density lipoprotein modified by mieloperoxidase in inflammatory pathways and Clinical studies. Mediators of Inflammation, 2013, 1-18.

[10] 10. Ehrenwald, E. & Fox, P. (1995). Role of endogenous ceruloplasmin in low density lipoprotein oxidation by human U937 monocytic cells. J.Clin. Invest, 97, 3, 884-890.

[11] 11. Ehrenwald, E., Chisolm, G. & Fox, P. (1994). Intact human ceruloplasmin oxidatively modifies low density lipoprotein. Biochem. J., 93, 1493-1501.

[12] 12. OLeary, V., Darley, V., Rusell, L. & Stone, D. (1992). Pro-oxidant effects of lipoxygenase-derived peroxides on the copper.initiated oxidation of low density lipoprotein. Biochem. J., 282, 631-634.

[13] 13. Satchell, L. & Leake, D. (2012). Oxidation of low-density lipoprotein by iron at lysosomal pH: implications for atherosclerosis. Biochemistry, 51, 3767-3775.

[14] 14. Parthasarathy, S., Raghavamenon, A., Garelnabi, M. & Santanam, N. (2010). Oxidized low-density lipoprotein. Methods Mol Biol, 610, 403-417.

[15] 15. Frostegard, J. (2013). Immunity, atherosclerosis and cardiovascular disease. BMC Medicine, 11, 117-129.

[16] 16. Silverstein, R., Li, W., Park, Y. & Raham, O. (2010). Mechanism of cell signaling by the scavenger receptor CD36: implications in atherosclerosis and thrombosis. Transactions of the American Clinical and Climatological Association, 121, 206- 220.

[17] 17. Paoletti, R., Gotto, A. & Hajjar, D. (2004). Inflammation in atherosclerosis and implications for therapy. Circulation, 109 (supplIII), III20-III26.

[18] 18. Chang, S. H, Johns, M., Boyle, J., McConnell, E., Kirkham, P., Bicknell C., et al. (2012). Model IgG monoclonal autoantibody-anti-idiotype pair for dissecting the humoral immmune response to oxidized low density lipoprotein. Hybridoma, 31, 2, 87-98.

[19] 19. Virella, G. & Lopes, M. (2008). Atherogenesis and the humoral response to modified lipoproteins. Atherosclerosis, 200, 2, 239-246.

[20] 20. Horkko, S., Bird, D., Miller, E., Itabe, H., Leitinger, N., Subbanagounder, G., Berliner, J., et al. (1999). Monoclonal antibodies specific for oxidized phospholipids or oxidized phospholipid-protein adducts inhibit macrophage uptake of oxidized low- density lipoproteins. The Journal of Clinical Investigation, 103, 1, 117-129.

[21] 21. Davignon, J. & Ganz, P. (2004). Role of endothelial dysfunction in atherosclerosis. Circulation, 109 (supplIII), III-27 III-32.

[22] 22. Wang, W., Hein, T., Zhang, C., Zawieja, D., Liao, J. & Kuo, L. (2011). Oxidized low- density lipoprotein inhibits oxide-mediated coronary arteriolar dilation by up- regulating endotelial arginase I. Microcirculation, 18, 1, 36-45.

[23] 23. Westhorpe, C., Dufour, E., Maisa, A., Jaworowski, A., Crowe, S. & Muller, W. (2012). Endothelial cell activation promotes foam cell formation by monocytes following transendothelial migration in an in vitro model. Exp Mol Pathol, 93, 2, 220-226.

[24] 24. Chen, J., Liu, Y., Hermonat, P. & Mehta, J. (2006). Lectin-like oxidized low-density lipoprotein receptor-1 (LOX- 1) transcriptional regulation by Oct-1 in human endotelial cells: implications for atherosclerosis. Biochem. J., 393, 255-265.

[25] 25. Dong, Q., Xiang, R., Zhang, D. & Qin, S. (2013). OX-LDL increases OX40L in endotelial cells through a LOX-1 dependent mechanism. Brazilian Journal of Medical and Biological Research, 46, 765-770.

[26] Cardiovasc Drugs, 25, 379-39

[27] 27. Huang, Y., Hu, Y., Mai, W., Cai, X., Song, Y., Wu, Y., et al. (2011). Plasma oxidized low- density lipoprotein is an independent risk factor in Young patients with coronary disease. Disease Markers, 31, 295-301.

[28] 28.Park, Y., Drazba, J., Vasanji, A., Egelhoff, T., Febbraio, M. & Silverstein, R. (2012). Oxidized LDL/CD36 interaction induces loss of cell polarity and inhibits macrophage locomotion. Molecular Biology of the Cell, 23, 3057-3068.

[29] 29. Go, G. W. & Mani, A. (2012). Low-density lipoprotein receptor (LDLR) Family orchestrates cholesterol homeostasis. Yale Journal of Biology and Medicine, 85, 19-28.

[30] 30. Ding, Z., Liu, S., Yang, B., Fan, Y. & Deng, X. (2012). Effect of oxidized low-density lipoprotein concentration polarization on human smooth muscle cells, proliferation, cycle, apoptosis and ozidized low-density lipoprotein uptake J. R. Soc. Interface, 9, 1233-1240.

[31] 31. Yu, J., Li, Y., Li, M., Qu, Z., & Ruan, Q. (2010). Oxidized low-density lipoprotein- induced transdefferentiation of bone marrow-derived smooth muscle-like cells into foam-like cells in vitro. Int. J. Exp. Path, 91, 24-33.

[32] 32. Moore, K. & Tabas, I. (2011). The cellular biology of macrophages in atherosclerosis. Cell, 145, 3, 341-355.

[33] 33. Maiolino, G., Rossitto, G., Caielli, P., Bisogni, V., Rossi, G. & Caló, L. (2013). The role of oxidized lo-density lipoproteins in atherosclerosis: the myths and the facts. Mediators of Inflammation, 2013, 1-13.

[34] 34. Asgary, S., Saberi, S. A. & Azampanah, S. (2007). Effect of immunization against ox- LDL with two different antgens on formation and Development of atherosclerosis. BioMed, 6,1, 32-37.

[35] 35. Huang, H., Mai, W., Liu, D., Hao, Y., Tao, J. & Dong, Y. (2008). The oxidation ratio of LDL: a predictor for coronary artery disease. Disease Markers, 24, 341-349.

[36] 36. Aoki, T., Abe, T., Yamada, E., Matsuto, T. & Okada, M. (2012). Increased LDL susceptibility to oxidation accelerates future carotid srtery atherosclerosis. Lipids in Health an Disease,11, 4-10.

[37] 37. Zuliani, G., Morieri, M., Volpato, S., Vigna, G., Bosi, C., Maggio, M., et al. (2013). Determinants and clinical significance of plasma oxidized LDLs in older individuals. A years follow-up study. Atherosclerosis, 226, 1, 201-207.

[38] 38. Dong, Y., Zhang, M., Wang, S., Liang, B., Zhao, Z., Liu, C., et al. (2010). Activation of AMP-activated Protein Kinase inhibits oxidized LDL-triggered endoplasmic reticulum stress in vivo. Diabetes, 59, 1386-1396.

LDL oxidada y la aterosclerosis

Resúmenes

Referencias bibliográficas

Fechas de Publicación

Histórico