High-density lipoprotein is a potential life saving antiatherogenic molecule. However, not all HDL is function-ally similar, it can become dysfunctional and may increase atherosclerotic risk. At present, it is unknown, which structural alterations of HDL are essential accounting for its defective functionality and the precise pro-atherogenic mechanisms of action. This study is aimed at identification of the possible prevalence of dysfunctional HDL in subjects and its composi-tional and functional characterization in comparison to that of functional HDL. HDL was isolated from serum by ultracentrifugation and subjected to functional assays. HDL from majority of healthy subjects showed remarkable antioxidant property by inhibiting LDL oxidation. However, in those healthy subjects with systemic oxidative stress and inflammatory response as well as in those with known coronary heart disease, HDL was dysfunctional and promoted LDL oxidation. Dysfunctional HDL was truly pro-oxidant as it induced intracellular reactive oxygen species formation in cultured monocytes/macrophages. Functional deficiency in HDL did not show any association with HDL-cholesterol content. However, its characterization showed an enrichment of triglycerides, phospholipids, lipid peroxides, and diminished activity of paraoxonase-1, compared to functional HDL, which might render the particle dysfunctional and pro-oxidant.This study demonstrates the prevalence of dysfunctional HDL even among healthy subjects, despite normal HDL-C level, and in majority of subjects with known CHD, which is pro-oxidant in nature that might promote vascular inflammation and atherogenesis. The functional assay of HDL could lead to improved predictive accuracy of cardiovascular disease risk associated with circulating HDL.
| Published in | International Journal of Nutrition and Food Sciences (Volume 2, Issue 3) |
| DOI | 10.11648/j.ijnfs.20130203.11 |
| Page(s) | 92-101 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2013. Published by Science Publishing Group |
Atherosclerosis, Inflammation, HDL-Function, Pro-Oxidant
| [1] | N. Ahmad, R. Bhopal, Is coronary heart disease rising in India? A systematic review based on ECG defined coronary heart disease, Heart, 91 (2005) 719-725. |
| [2] | G.K. Hansson, Inflammation, atherosclerosis, and coronary artery disease, N Engl J Med, 352 (2005) 1685-1695. |
| [3] | P.J. Barter, S. Nicholls, K.A. Rye, G.M. Anantharamaiah, M. Navab, A.M. Fogelman, Antiinflammatory properties of HDL, Circ Res, 95 (2004) 764-772. |
| [4] | P.P. Toth, High-density lipoprotein and cardiovascular risk, Circulation, 109 (2004) 1809-1812. |
| [5] | A.M. Gotto, Jr., E.A. Brinton, Assessing low levels of high-density lipoprotein cholesterol as a risk factor in coronary heart disease: a working group report and update, J Am Coll Cardiol, 43 (2004) 717-724. |
| [6] | H.B. G, V.S. Rao, V.V. Kakkar, Friend Turns Foe: Trans-formation of Anti-Inflammatory HDL to Proinflammatory HDL during Acute-Phase Response, Cholesterol, 2011 (2011) 274629. |
| [7] | A.A. Baron, S.B. Baron, High levels of HDL cholesterol do not predict protection from cardiovascular disease in women, Prev Cardiol, 10 (2007) 125-127. |
| [8] | E. Eren, N. Yilmaz, O. Aydin, High Density Lipoprotein and it's Dysfunction, Open Biochem J, 6 (2012) 78-93. |
| [9] | F. Paneni, F. Cosentino, F. Marrara, F. Palano, G. Capretti, M. Gregori, G. Tocci, M. Testa, M. Volpe, The clinical relevance of dysfunctional HDL in patients with coronary artery disease: a 3-year follow-up study, Int J Cardiol, 158 (2012) 158-160. |
| [10] | S. Dodani, Excess coronary artery disease risk in South Asian immigrants: can dysfunctional high-density lipoprotein explain increased risk?, Vasc Health Risk Manag, 4 (2008) 953-961. |
| [11] | M. McMahon, J. Grossman, B. Skaggs, J. Fitzgerald, L. Sahakian, N. Ragavendra, C. Charles-Schoeman, K. Watson, W.K. Wong, E. Volkmann, W. Chen, A. Gorn, G. Karpouzas, M. Weisman, D.J. Wallace, B.H. Hahn, Dysfunctional proinflammatory high-density lipoproteins confer increased risk of atherosclerosis in women with systemic lupus ery-thematosus, Arthritis Rheum, 60 (2009) 2428-2437. |
| [12] | R. Asleh, S. Blum, S. Kalet-Litman, J. Alshiek, R. Miller-Lotan, R. Asaf, W. Rock, M. Aviram, U. Milman, C. Shapira, Z. Abassi, A.P. Levy, Correction of HDL dysfunction in in-dividuals with diabetes and the haptoglobin 2-2 genotype, Diabetes, 57 (2008) 2794-2800. |
| [13] | V.S. Soumyarani, N. Jayakumari, Oxidatively modified high density lipoprotein promotes inflammatory response in hu-man monocytes-macrophages by enhanced production of ROS, TNF-alpha, MMP-9, and MMP-2, Mol Cell Biochem, 366 (2012) 277-285. |
| [14] | N. Jayakumari, G. Thejaseebai, High prevalence of low serum paraoxonase-1 in subjects with coronary artery disease, J Clin Biochem Nutr, 45 (2009) 278-284. |
| [15] | H. Mirjafari, A. Al-Husain, I.N. Bruce, Cardiovascular risk factors in inflammatory arthritis, Curr Opin Lipidol, 22 (2011) 296-301. |
| [16] | E. Regidor, J. Franch, M. Segui, R. Serrano, F. Rodriguez-Artalejo, S. Artola, Traditional Risk Factors Alone Could Not Explain the Excess Mortality in Patients With Diabetes: A national cohort study of Spanish older adults, Diabetes Care, (2012). |
| [17] | R. Ross, Atherosclerosis--an inflammatory disease, N Engl J Med, 340 (1999) 115-126. |
| [18] | P. Libby, Inflammation in atherosclerosis, Nature, 420 (2002) 868-874. |
| [19] | E. Zouridakis, P. Avanzas, R. Arroyo-Espliguero, S. Frede-ricks, J.C. Kaski, Markers of inflammation and rapid coro-nary artery disease progression in patients with stable angina pectoris, Circulation, 110 (2004) 1747-1753. |
| [20] | P.M. Ridker, C.H. Hennekens, B. Roitman-Johnson, M.J. Stampfer, J. Allen, Plasma concentration of soluble intercel-lular adhesion molecule 1 and risks of future myocardial in-farction in apparently healthy men, Lancet, 351 (1998) 88-92. |
| [21] | A.T. Remaley, M. Amar, D. Sviridov, HDL-replacement therapy: mechanism of action, types of agents and potential clinical indications, Expert Rev Cardiovasc Ther, 6 (2008) 1203-1215. |
| [22] | C. Izzo, F. Grillo, E. Murador, Improved method for deter-mination of high-density-lipoprotein cholesterol I. Isolation of high-density lipoproteins by use of polyethylene glycol 6000, Clin Chem, 27 (1981) 371-374. |
| [23] | G. Gallou, A. Ruelland, B. Legras, D. Maugendre, H. Al-lannic, L. Cloarec, Plasma malondialdehyde in type 1 and type 2 diabetic patients, Clin Chim Acta, 214 (1993) 227-234. |
| [24] | N. Jayakumari, V. Ambikakumari, K.G. Balakrishnan, K.S. Iyer, Antioxidant status in relation to free radical production during stable and unstable anginal syndromes, Atheroscle-rosis, 94 (1992) 183-190. |
| [25] | S.T. Omaye, J.D. Turnbull, H.E. Sauberlich, Selected me-thods for the determination of ascorbic acid in animal cells, tissues, and fluids, Methods Enzymol, 62 (1979) 3-11. |
| [26] | M. Toth, A. Sohail, R. Fridman, Assessment of gelatinases (MMP-2 and MMP-9) by gelatin zymography, Methods Mol Biol, 878 (2012) 121-135. |
| [27] | M.J. Chapman, S. Goldstein, D. Lagrange, P.M. Laplaud, A density gradient ultracentrifugal procedure for the isolation of the major lipoprotein classes from human serum, J Lipid Res, 22 (1981) 339-358. |
| [28] | J.R. Dulley, P.A. Grieve, A simple technique for eliminating interference by detergents in the Lowry method of protein determination, Anal Biochem, 64 (1975) 136-141. |
| [29] | K. Lorentz, B. Flatter, E. Augustin, Arylesterase in serum: elaboration and clinical application of a fixed-incubation method, Clin Chem, 25 (1979) 1714-1720. |
| [30] | M. Navab, S.Y. Hama, G.P. Hough, G. Subbanagounder, S.T. Reddy, A.M. Fogelman, A cell-free assay for detecting HDL that is dysfunctional in preventing the formation of or inac-tivating oxidized phospholipids, J Lipid Res, 42 (2001) 1308-1317. |
| [31] | S. Jovinge, M.P. Ares, B. Kallin, J. Nilsson, Human mono-cytes/macrophages release TNF-alpha in response to Ox-LDL, Arterioscler Thromb Vasc Biol, 16 (1996) 1573-1579. |
| [32] | C. Charles-Schoeman, J. Watanabe, Y.Y. Lee, D.E. Furst, S. Amjadi, D. Elashoff, G. Park, M. McMahon, H.E. Paulus, A.M. Fogelman, S.T. Reddy, Abnormal function of high-density lipoprotein is associated with poor disease control and an altered protein cargo in rheumatoid arthritis, Arthritis Rheum, 60 (2009) 2870-2879. |
| [33] | J.M. Lee, R.P. Choudhury, Atherosclerosis regression and high-density lipoproteins, Expert Rev Cardiovasc Ther, 8 (2010) 1325-1334. |
| [34] | M. Navab, S.T. Reddy, B.J. Van Lenten, A.M. Fogelman, HDL and cardiovascular disease: atherogenic and athero-protective mechanisms, Nat Rev Cardiol, 8 (2011) 222-232. |
| [35] | B.J. Ansell, M. Navab, S. Hama, N. Kamranpour, G. Fona-row, G. Hough, S. Rahmani, R. Mottahedeh, R. Dave, S.T. Reddy, A.M. Fogelman, Inflammatory/antiinflammatory properties of high-density lipoprotein distinguish patients from control subjects better than high-density lipoprotein cholesterol levels and are favorably affected by simvastatin treatment, Circulation, 108 (2003) 2751-2756. |
| [36] | S. Manzi, E.N. Meilahn, J.E. Rairie, C.G. Conte, T.A. Medsger, Jr., L. Jansen-McWilliams, R.B. D'Agostino, L.H. Kuller, Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study, Am J Epidemiol, 145 (1997) 408-415. |
| [37] | M. Navab, G.M. Ananthramaiah, S.T. Reddy, B.J. Van Len-ten, B.J. Ansell, S. Hama, G. Hough, E. Bachini, V.R. Gri-jalva, A.C. Wagner, Z. Shaposhnik, A.M. Fogelman, The double jeopardy of HDL, Ann Med, 37 (2005) 173-178. |
| [38] | T. Itoh, H. Matsuda, M. Tanioka, K. Kuwabara, S. Itohara, R. Suzuki, The role of matrix metalloproteinase-2 and matrix metalloproteinase-9 in antibody-induced arthritis, J Immunol, 169 (2002) 2643-2647. |
| [39] | Z.S. Galis, J.J. Khatri, Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly, Circ Res, 90 (2002) 251-262. |
| [40] | E. Rodrigo, M. Lopez-Hoyos, R. Escallada, G. Fernandez-Fresnedo, J.C. Ruiz, C. Pinera, J.G. Cotorruelo, J.A. Zubi-mendi, A.L. de Francisco, M. Arias, Circulating levels of matrix metalloproteinases MMP-3 and MMP-2 in renal transplant recipients with chronic transplant nephropathy, Nephrol Dial Transplant, 15 (2000) 2041-2045. |
| [41] | S. Takeshita, T. Tokutomi, H. Kawase, K. Nakatani, H. Tsu-jimoto, Y. Kawamura, I. Sekine, Elevated serum levels of matrix metalloproteinase-9 (MMP-9) in Kawasaki disease, Clin Exp Immunol, 125 (2001) 340-344. |
| [42] | P. Kampus, P. Muda, J. Kals, T. Ristimae, K. Fischer, R. Teesalu, M. Zilmer, The relationship between inflammation and arterial stiffness in patients with essential hypertension, Int J Cardiol, 112 (2006) 46-51. |
| [43] | J.D. Smith, Dysfunctional HDL as a diagnostic and thera-peutic target, Arterioscler Thromb Vasc Biol, 30 (2010) 151-155. |
| [44] | N. Yilmaz, Relationship between paraoxonase and homo-cysteine: crossroads of oxidative diseases, Arch Med Sci, 8 (2012) 138-153. |
| [45] | M. Navab, S.Y. Hama, C.J. Cooke, G.M. Anantharamaiah, M. Chaddha, L. Jin, G. Subbanagounder, K.F. Faull, S.T. Reddy, N.E. Miller, A.M. Fogelman, Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: step 1, J Lipid Res, 41 (2000) 1481-1494. |
| [46] | M. Navab, S.Y. Hama, G.M. Anantharamaiah, K. Hassan, G.P. Hough, A.D. Watson, S.T. Reddy, A. Sevanian, G.C. Fonarow, A.M. Fogelman, Normal high density lipoprotein inhibits three steps in the formation of mildly oxidized low density lipoprotein: steps 2 and 3, J Lipid Res, 41 (2000) 1495-1508. |
| [47] | D.L. Sparks, W.S. Davidson, S. Lund-Katz, M.C. Phillips, Effects of the neutral lipid content of high density lipoprotein on apolipoprotein A-I structure and particle stability, J Biol Chem, 270 (1995) 26910-26917. |
| [48] | V. Zago, S. Sanguinetti, F. Brites, G. Berg, J. Verona, F. Basilio, R. Wikinski, L. Schreier, Impaired high density li-poprotein antioxidant activity in healthy postmenopausal women, Atherosclerosis, 177 (2004) 203-210. |
| [49] | D. Deepa, N. Jayakumari, S.V. Thomas, Oxidative stress is increased in women with epilepsy: Is it a potential mechanism of anti-epileptic drug-induced teratogenesis?, Ann Indian Acad Neurol, 15 (2012) 281-286. |
APA Style
S. Sini., N. Jayakumari. (2013). Functionally Defective High Density Lipoprotein is Pro-Oxidant: a Deviation from Normal Atheroprotective Character. International Journal of Nutrition and Food Sciences, 2(3), 92-101. https://doi.org/10.11648/j.ijnfs.20130203.11
ACS Style
S. Sini.; N. Jayakumari. Functionally Defective High Density Lipoprotein is Pro-Oxidant: a Deviation from Normal Atheroprotective Character. Int. J. Nutr. Food Sci. 2013, 2(3), 92-101. doi: 10.11648/j.ijnfs.20130203.11
AMA Style
S. Sini., N. Jayakumari. Functionally Defective High Density Lipoprotein is Pro-Oxidant: a Deviation from Normal Atheroprotective Character. Int J Nutr Food Sci. 2013;2(3):92-101. doi: 10.11648/j.ijnfs.20130203.11
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Download@article{10.11648/j.ijnfs.20130203.11,
author = {S. Sini. and N. Jayakumari},
title = {Functionally Defective High Density Lipoprotein is Pro-Oxidant: a Deviation from Normal Atheroprotective Character},
journal = {International Journal of Nutrition and Food Sciences},
volume = {2},
number = {3},
pages = {92-101},
doi = {10.11648/j.ijnfs.20130203.11},
url = {https://doi.org/10.11648/j.ijnfs.20130203.11},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijnfs.20130203.11},
abstract = {High-density lipoprotein is a potential life saving antiatherogenic molecule. However, not all HDL is function-ally similar, it can become dysfunctional and may increase atherosclerotic risk. At present, it is unknown, which structural alterations of HDL are essential accounting for its defective functionality and the precise pro-atherogenic mechanisms of action. This study is aimed at identification of the possible prevalence of dysfunctional HDL in subjects and its composi-tional and functional characterization in comparison to that of functional HDL. HDL was isolated from serum by ultracentrifugation and subjected to functional assays. HDL from majority of healthy subjects showed remarkable antioxidant property by inhibiting LDL oxidation. However, in those healthy subjects with systemic oxidative stress and inflammatory response as well as in those with known coronary heart disease, HDL was dysfunctional and promoted LDL oxidation. Dysfunctional HDL was truly pro-oxidant as it induced intracellular reactive oxygen species formation in cultured monocytes/macrophages. Functional deficiency in HDL did not show any association with HDL-cholesterol content. However, its characterization showed an enrichment of triglycerides, phospholipids, lipid peroxides, and diminished activity of paraoxonase-1, compared to functional HDL, which might render the particle dysfunctional and pro-oxidant.This study demonstrates the prevalence of dysfunctional HDL even among healthy subjects, despite normal HDL-C level, and in majority of subjects with known CHD, which is pro-oxidant in nature that might promote vascular inflammation and atherogenesis. The functional assay of HDL could lead to improved predictive accuracy of cardiovascular disease risk associated with circulating HDL.},
year = {2013}
}
TY - JOUR T1 - Functionally Defective High Density Lipoprotein is Pro-Oxidant: a Deviation from Normal Atheroprotective Character AU - S. Sini. AU - N. Jayakumari Y1 - 2013/05/02 PY - 2013 N1 - https://doi.org/10.11648/j.ijnfs.20130203.11 DO - 10.11648/j.ijnfs.20130203.11 T2 - International Journal of Nutrition and Food Sciences JF - International Journal of Nutrition and Food Sciences JO - International Journal of Nutrition and Food Sciences SP - 92 EP - 101 PB - Science Publishing Group SN - 2327-2716 UR - https://doi.org/10.11648/j.ijnfs.20130203.11 AB - High-density lipoprotein is a potential life saving antiatherogenic molecule. However, not all HDL is function-ally similar, it can become dysfunctional and may increase atherosclerotic risk. At present, it is unknown, which structural alterations of HDL are essential accounting for its defective functionality and the precise pro-atherogenic mechanisms of action. This study is aimed at identification of the possible prevalence of dysfunctional HDL in subjects and its composi-tional and functional characterization in comparison to that of functional HDL. HDL was isolated from serum by ultracentrifugation and subjected to functional assays. HDL from majority of healthy subjects showed remarkable antioxidant property by inhibiting LDL oxidation. However, in those healthy subjects with systemic oxidative stress and inflammatory response as well as in those with known coronary heart disease, HDL was dysfunctional and promoted LDL oxidation. Dysfunctional HDL was truly pro-oxidant as it induced intracellular reactive oxygen species formation in cultured monocytes/macrophages. Functional deficiency in HDL did not show any association with HDL-cholesterol content. However, its characterization showed an enrichment of triglycerides, phospholipids, lipid peroxides, and diminished activity of paraoxonase-1, compared to functional HDL, which might render the particle dysfunctional and pro-oxidant.This study demonstrates the prevalence of dysfunctional HDL even among healthy subjects, despite normal HDL-C level, and in majority of subjects with known CHD, which is pro-oxidant in nature that might promote vascular inflammation and atherogenesis. The functional assay of HDL could lead to improved predictive accuracy of cardiovascular disease risk associated with circulating HDL. VL - 2 IS - 3 ER -
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