Current Science

Open Access Open Access  Restricted Access Subscription Access

Oxidized Lipoproteins as the Diagnostic Target for Cardiovascular Diseases


Affiliations
1 Pushpagiri Research Centre, Pushpagiri Institute of Medical Sciences and Research Centre, Thiruvalla 689 101, India
2 The CHILDS Trust Medical Research Foundation, Chennai 600 034, India
3 Centre for Bio-separation Technology, VIT University, Vellore 632 014, India
 

Low HDL-cholesterol and high LDL-cholesterol in plasma have long been associated with cardiovascular disease (CVD) risk. The quantity of cholesterol associated with these lipoproteins is being traditionally used to predict CVD risk. However, recent studies have suggested that the quality and functionality of these lipoproteins are more important. The lipoproteins - HDL and LDL - undergo both enzymatic and non-enzymatic modifications which impair their functional capability and hence, test of such modification which reflects the quality of HDL can be a good predictor of CVD risk. The present article discusses oxidation- associated dysfunctionality of lipoproteins and their potential in laboratory diagnosis of CVD.

Keywords

Cardiovascular Disease, Cholesterol, Diagnostic Target, Oxidized Lipoproteins.
User
Notifications
Font Size

  • Benjamin, E. J. et al., American heart association statistics committee and stroke statistics subcommittee. Heart disease and stroke statistics - 2017 update: a report from the American Heart Association. Circulation, 2017, 135(10), e146-e603; doi: 10.1161/CIR.0000000000000485.

  • Fuster, V. and Kelly, B. B. (eds), Institute of Medicine (US) Committee on Preventing the Global Epidemic of Cardiovascular Disease: Meeting the Challenges in Developing Countries, Promoting Cardiovascular Health in the Developing World: a Critical Challenge to Achieve Global Health, National Academic Press (US), Washington, DC, 2010.

  • Gupta, R., Mohan, I. and Narula, J., Trends in coronary heart disease epidemiology in India. Ann. Glob. Health, 2016, 82(2), 307315; doi:10.1016/j.aogh.2016.04.002. Review. PubMed PMID: 27372534.

  • Gupta, R., Guptha, S., Sharma, K. K., Gupta, A. and Deedwania, P., Regional variations in cardiovascular risk factors in India: India heart watch. World J. Cardiol., 2012, 4(4), 112-120; doi:10.4330/wjc.v4.i4.112.

  • Folsom, A. R., Classical and novel biomarkers for cardiovascular risk prediction in the United States. J. Epidemiol., 2013, 23(3), 158-162; doi:10.2188/jea.JE20120157.

  • Paynter, N. P., Everett, B. M. and Cook, N. R., Cardiovascular disease risk prediction in women: is there a role for novel biomarkers? Clin. Chem., 2014, 60(1), 88-97; doi: 10.1373/clinchem.2013.202796. Review. PubMed PMID: 24100805; PubMed Central PMCID: PMC3877731.

  • Fisher, W. R., The structure of the lower-density lipoproteins of human plasma: newer concepts derived from studies with the analytical ultracentrifuge. Ann. Clin. Lab. Sci., 1972, 2, 198-208.

  • Brown, M. S., Kovanen, P. T. and Goldstein, J. L., Regulation of plasma cholesterol by lipoprotein receptors. Science, 1981, 212, 628-635.

  • Hegele, R. A., Plasma lipoproteins: genetic influences and clinical implications. Nature Rev. Genet., 2009, 10, 109-121.

  • Ben, J., Zhu, X., Zhang, H. and Chen, Q., Class A1 scavenger receptors in cardiovascular diseases. Br. J. Pharmacol., 2015, 172(23), 5523-5530; doi:10.1111/bph.13105.

  • Witztum, J. L. and Steinberg, D., Role of oxidized low density lipoprotein in atherogenesis. J. Clin. Invest., 1991, 88(6), 1785-1792. Review. PubMed PMID: 1752940; PubMed Central PMCID: PMC295745.

  • Castelao, J. E. and Gago-Dominguez, M., Risk factors for cardiovascular disease in women: relationship to lipid peroxidation and oxidative stress. Med. Hypotheses, 2008, 71(1), 39-44.

  • Parthasarathy, S., Raghavamenon, A., Garelnabi, M. O. and Santanam, N., Oxidized low-density lipoprotein. Methods Mol. Biol., 201, 610, 403-417; doi:10.1007/978-1-60327-029-8_24.

  • Noguchi, N., Novel insights into the molecular mechanisms of the antiatherosclerotic properties of antioxidants: the alternatives to radical scavenging. Free Radic. Biol. Med., 2002, 33(11), 1480-1489. Review. PubMed PMID: 12446205.

  • Yoshida, H. and Kisugi, R., Mechanisms of LDL oxidation. Clin. Chim. Acta, 2010, 411(23-24), 875-882; doi:10.1016/j.cca.2010.08.038. Review. PubMed PMID: 20816951.

  • Malle, E., Marsche, G., Arnhold, J. and Davies, M. J., Modification of low-density lipoprotein by myeloperoxidase-derived oxidants and reagent hypochlorous acid. Biochim. Biophys. Acta, 2006, 1761(4), 392-415. PubMed PMID: 16698314.

  • Delporte, C. et al., Impact of myeloperoxidase-LDL interactions on enzyme activity and subsequent posttranslational oxidative modifications of apoB-100. J. Lipid Res., 2014, 55(4), 747-757; doi:10.1194/jlr.M047449. PubMed PMID: 24534704.

  • Reaven, P. D. and Witztum, J. L., Oxidized low density lipoproteins in atherogenesis: role of dietary modification. Annu. Rev. Nutr., 1996, 16, 51-71. Review. PubMed PMID: 8839919.

  • Miller, Y. I., Choi, S. H., Fang, L. and Tsimikas, S., Lipoprotein modification and macrophage uptake: role of pathologic cholesterol transport in atherogenesis. Subcell. Biochem., 2010, 51, 229-251; doi: 10.1007/978-90-481-8622-8_8. Review. PubMed PMID: 20213546.

  • Hoff, H. F., Zyromski, N., Armstrong, D. and O’Neil, J., Aggregation as well as chemical modification of LDL during oxidation is responsible for poor processing in macrophages. J. Lipid Res., 1993, 34(11), 1919-1929. PubMed PMID: 8263416.

  • Delporte, C., Van Antwerpen, P., Vanhamme, L., Roumeguere, T. and Zouaoui Boudjeltia, K., Low-density lipoprotein modified by myeloperoxidase in inflammatory pathways and clinical studies. Mediat. Inflamm, 2013, 2013, 971579; doi:10.1155/2013/971579. Review. PubMed PMID: 23983406; PubMed Central PMCID: PMC3742028.

  • Oram, J. F. and Heinecke, J. W., ATP-binding cassette transporter A1: a cell cholesterol exporter that protects against cardiovascular disease. Physiol. Rev., 2005, 85, 1343-1372.

  • Navab, M., Hama, S. Y., Hough, G. P., Subbanagounder, G., Reddy, S. T. and Fogelman, A. M., A cell-free assay for detecting HDL that is dysfunctional in preventing the formation of or inactivating oxidized phospholipids. J. Lipid Res., 2001, 42(8), 1308-1317.

  • Vaziri, N. D., Moradi, H., Pahl, M. V., Fogelman, A. M. and Navab, M., In vitro stimulation of HDL anti-inflammatory activity and inhibition of LDL pro-inflammatory activity in the plasma of patients with end-stage renal disease by an ApoA-1 mimetic peptide. Kidney Int., 2009, 76(4), 437-444; doi:10.1038/ki.2009.177.

  • Florentin, M., Liberopoulos, E. N., Wierzbicki, A. S. and Mikhailidis, D. P., Multiple actions of high-density lipoprotein. Curr. Opin. Cardiol., 2008, 23(4), 370-378; doi: 10.1097/HC0.0b013e3283043806. Review. PubMed PMID: 18520722.

  • Hao, W. and Friedman, A., The LDL-HDL profile determines the risk of atherosclerosis: a mathematical model. PLoS ONE, 2014, 9(3), e90497; doi:10.1371/journal.pone.0090497. PubMed PMID: 24621857.

  • Ferretti, G., Bacchetti, T., Negre-Salvayre, A., Salvayre, R., Dousset, N. and Curatola, G., Structural modifications of HDL and functional consequences. Atherosclerosis, 2006, 184, 1-7. PubMed PMID: 16157342.

  • Francis, G. A., High density lipoprotein oxidation: in vitro susceptibility and potential in vivo consequences. Biochim. Biophys. Acta, 2000, 1483, 217-235. PubMed PMID: 10634938.

  • Heinecke, J. W., Rosen, H. and Chait, A., Iron and copper promote modification of low density lipoprotein by human arterial smooth muscle cells in culture. J. Clin. Invest., 1984, 74(5), 1890-1894.

  • Lamb, D. J., Mitchinson, M. J. and Leake, D. S., Transition metal ions within human atherosclerotic lesions can catalyse the oxidation of low density lipoprotein by macrophages. FEBS Lett., 1995, 374(1), 12-16. PubMed PMID: 7589497.

  • Arai, H., Berlett, B. S., Chock, P. B. and Stadtman, E. R., Effect of bicarbonate on iron-mediated oxidation of low-density lipoprotein. Proc. Natl. Acad. Sci. USA, 2005, 102(30), 10472-10477. PubMed PMID: 16027354; PubMed Central PMCID: PMC1176232.

  • Morgan, J. and Leake, D. S., Oxidation of low density lipoprotein by iron or copper at acidic pH. J. Lipid Res., 1995, 36(12), 2504-2512. PubMed PMID: 8847477.

  • Leake, D. S., Does an acidic pH explain why low density lipoprotein is oxidised in atherosclerotic lesions? Atherosclerosis, 1997, 129(2), 149-157. Review. PubMed PMID: 9105556.

  • Yoshida, H. and Kisugi, R., Mechanisms of LDL oxidation. Clin. Chim. Acta, 2010, 411(23-24), 1875-1882; doi:10.1016/j.cca.2010.08.038. PubMed PMID: 20816951.

  • Boullier, A. et al., Minimally oxidized LDL offsets the apoptotic effects of extensively oxidized LDL and free cholesterol in macrophages. Arterioscler. Thromb. Vasc. Biol., 2006, 26(5), 1169-1176. PubMed PMID: 16484596.

  • Yamamoto, S., Mammalian lipoxygenases: molecular structures and functions. Biochim. Biophys. Acta, 1992, 1128(2-3), 117-131. PubMed PMID: 1420284.

  • Parthasarathy, S., Wieland, E. and Steinberg, D., A role for endothelial cell lipoxygenase in the oxidative modification of low density lipoprotein. Proc. Natl. Acad. Sci. USA, 1989, 86, 1046-1050.

  • Huo, Y. et al., Critical role of macrophage 12/15-lipoxygenase for atherosclerosis in apolipoprotein E-deficient mice. Circulation, 2004, 110(14), 2024-2031. PubMed PMID: 15451785.

  • Kuhn, H., Romisch, I. and Belkner, J., The role of lipoxygenaseisoforms in atherogenesis. Mol. Nutr. Food Res., 2005, 49(11), 1014-1029. PubMed PMID: 16270276.

  • Shen, J. et al., Macrophage-mediated 15-lipoxygenase expression protects against atherosclerosis development. J. Clin. Invest., 1996, 98(10), 2201-2208.

  • Shen, J., Kuhn, H., Petho-Schramm, A. and Chan, L., Transgenic rabbits with the integrated human 15-lipoxygenase gene driven by a lysozyme promoter: macrophage-specific expression and variable positional specificity of the transgenic enzyme. FASEB J., 1995, 9(15), 1623-1631. PubMed PMID: 8529842.]

  • Merched, A. J., Ko, K., Gotlinger, K. H., Serhan, C. N. and Chan, L., Atherosclerosis: evidence for impairment of resolution of vascular inflammation governed by specific lipid mediators. FASEB J., 2008, 22(10), 3595-3606; doi:10.1096/fj.08-112201.

  • George, J. et al., 12/15-Lipoxygenase gene disruption attenuates atherogenesis in LDL receptor-deficient mice. Circulation, 2001, 104(14), 1646-1650. PubMed PMID: 11581143.

  • Cyrus, T. et al., Absence of 12/15-lipoxygenase expression decreases lipid peroxidation and atherogenesis in apolipoprotein e-deficient mice. Circulation, 2001, 103(18), 2277-2282. PubMed PMID: 11342477.

  • Sukhanov, S. et al., Insulin-like growth factor I reduces lipid oxidation and foam cell formation via downregulation of 12/15lipoxygenase. Atherosclerosis, 2015, 238(2), 313-320; doi: 10.1016/j.atherosclerosis.2014.12.024.

  • Wuest, S. J., Crucet, M., Gemperle, C., Loretz, C. and Hersberger, M. Expression and regulation of 12/15-lipoxygenases in human primary macrophages. Atherosclerosis, 2015, 225(1), 121-127; doi:10.1016/j.atherosclerosis.2012. 07.022.

  • Schindhelm, R. K., van der Zwan, L. P., Teerlink, T. and Scheffer, P. G., Myeloperoxidase: a useful biomarker for cardiovascular disease risk stratification? Clin. Chem., 2009, 55, 1462-1470; doi: 10.1373/clinchem.2009.126029. Review. PubMed PMID: 19556446.

  • Meuwese, M. C. et al., Serum myeloperoxidase levels are associated with the future risk of coronary artery disease in apparently healthy individuals: the EPIC-Norfolk prospective population study. J. Am. Coll. Cardiol., 2007, 50(2), 159-165. PubMed PMID: 17616301.

  • Baldus, S. et al., Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes. Circulation, 2003, 108(12), 1440-1445. PubMed PMID: 12952835.

  • Carr, A. C., Myzak, M. C., Stocker, R., McCall, M. R. and Frei, B., Myeloperoxidase binds to low-density lipoprotein: potential implications for atherosclerosis. FEBS Lett., 2000, 487, 176-180.

  • Carr, A. C., McCall, M. R. and Frei, B., Oxidation of LDL by myeloperoxidase and reactive nitrogen species: reaction pathways and antioxidant protection. Arterioscler. Thromb. Vasc. Biol., 2000, 20, 1716-1723.

  • Chakraborty, S., Cai, Y. and Tarr, M. A., In vitro oxidative foot printing provides insight into apolipoprotein B-100 structure in low-density lipoprotein. Proteomics, 2014, 14(21-22), 2614-2622; doi:10.1002/pmic.201300174. PubMed PMID: 25176030.

  • Vicca, S. et al., New insights into the effects of the protein moiety of oxidized LDL (oxLDL). Kidney Int. Suppl., 2003, 84, S125-S127. Review. PubMed PMID: 12694326.

  • Heinecke, J. W., Mass spectrometric quantification of amino acid oxidation products in proteins: insights into pathways that promote LDL oxidation in the human artery wall. FASEB J., 1999, 13(10), 1113-1120. Review. PubMed PMID: 10385603.

  • Hazen, S. L. and Heinecke, J. W., 3-Chlorotyrosine, a specific marker of myeloperoxidase-catalyzed oxidation, is markedly elevated in low density lipoprotein isolated from human atherosclerotic intima. J. Clin. Invest., 1997, 99, 2075-2081.

  • Malle, E., Marsche, G., Arnhold, J. and Davies, M. J., Modification of low-density lipoprotein by myeloperoxidase-derived oxidants and reagent hypochlorous acid. Biochim. Biophys. Acta, 2006, 1761(4), 392-415.

  • Kotani, K., Maekawa, M., Kanno, T., Kondo, A., Toda, N. and Manabe, M., Distribution of immunoreactive malondialdehydemodified low-density lipoprotein in human serum. Biochim. Biophys. Acta, 1994, 1215(1-2), 121-125.

  • Delporte, C. et al., Impact of myeloperoxidase-LDL interactions on enzyme activity and subsequent posttranslational oxidative modifications of ApoB-100. J. Lipid Res., 2014, 55(4), 747-557.

  • Cuchel, M. and Rader, D. J., Macrophage reverse cholesterol transport: key to the regression of atherosclerosis? Circulation, 2006, 113(21), 2548-2555. PubMed PMID: 16735689.

  • Oram, J. F. and Lawn, R. M., ABCA1. The gatekeeper for eliminating excess tissue cholesterol. J. Lipid Res., 2001, 42(8), 1173-1179. PubMed PMID: 11483617.

  • Khera, A. V. et al., Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N. Engl. J. Med., 2011, 364, 127-135; doi:10.1056/NEJMoa1001689.

  • Rohatgi, A. et al., HDL cholesterol efflux capacity and incident cardiovascular events. N. Engl. J. Med., 2014, 371, 2383-2393; doi:10.1056/NEJMoa1409065.

  • Heinecke, J. W., Small HDL promotes cholesterol efflux by the ABCA1 pathway in macrophages: implications for therapies targeted to HDL. Circ. Res., 2015, 116(7), 1101-1103; doi:10.1161/CIRCRESAHA.115.306052. PubMed PMID: 25814677.

  • Florentin, M., Liberopoulos, E. N., Wierzbicki, A. S. and Mikhailidis, D. P., Multiple actions of high-density lipoprotein. Curr. Opin. Cardiol., 2008, 23(4), 370-378; doi: 10.1097/HC0.0b013e3283043806. Review. PubMed PMID: 18520722.

  • Ansell, B. J. et al., Inflammatory/anti-inflammatory properties of high-density lipoprotein distinguish patients from control subjects better than high-density lipoprotein cholesterol levels and are favourably affected by simvastatin treatment. Circulation, 2003, 108, 2751-2756. PubMed: 14638544.

  • Aviram, M., Rosenblat, M., Bisgaier, C. L., Newton, R. S., PrimoParmo, S. L. and La Du, B. N., Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. a possible peroxidative role for paraoxonase. J. Clin. Invest., 1998, 101(8), 1581-1590.

  • Shih, D. M. et al., Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature, 1998, 394(6690), 284-287.

  • Rosenblat, M., Volkova, N. and Aviram, M., Injection of paraoxonase 1 (P0N1) to mice stimulates their HDL and macrophage antiatherogenicity. Biofactors, 2011, 37(6), 462-467; doi:10.1002/biof.188. PubMed PMID: 22162319.

  • Fridman, O., Gariglio, L., Riviere, S., Porcile, R., Fuchs, A. and Potenzoni, M., Paraoxonase 1 gene polymorphisms and enzyme activities in coronary artery disease and its relationship to serum lipids and glycemia. Arch. Cardiol. Mex., 2016, 86(4), 350-357; doi:10.1016/j.acmx.2016.08.001. PubMed PMID: 27640339.

  • Shuhei, N., Soderlund, S., Jauhiainen, M. and Taskinen, M.-R., Effect of HDL composition and particle size on the resistance of HDL to the oxidation. Lipids Health Dis., 2010, 9, 104; doi:10.1186/1476-511X-9-104.

  • Vivekanandan-Giri, A. et al., High density lipoprotein is targeted for oxidation by myeloperoxidase in rheumatoid arthritis. Ann. Rheum. Dis., 2013, 72(10), 1725-1731; doi: 10.1136/annrheumdis-2012-202033.

  • Bergt, C., Oram, J. F. and Heinecke, J. W., Oxidized HDL: the paradoxidation of lipoproteins. Arterioscler. Thromb. Vasc. Biol., 2003, 23(9), 1488-1490. Review. PubMed PMID: 12972461.

  • Thomson, L., 3-Nitrotyrosine modified proteins in atherosclerosis. Dis. Markers, 2015, 2015, 8; doi:10.1155/2015/708282.

  • Panzenbock, U. and Stocker, R., Formation of methionine sulfoxidecontaining specific forms of oxidized high-density lipoproteins. Biochim. Biophys. Acta, 2005, 1703(2), 171-181. PubMed PMID: 15680225.

  • Holzer, M. et al., Protein carbamylation renders high-density lipoprotein dysfunctional. Antioxid. Redox Signal., 2011, 14(12), 2337-2346; doi: 10.1089/ars.2010.3640. PubMed PMID: 21235354.

  • Smith, J. D., Dysfunctional HDL as a diagnostic and therapeutic target. Arterioscler. Thromb. Vasc. Biol., 2010, 30(2), 151-155; doi:10.1161/ATVBAHA. 108.179226. PubMed PMID: 19679832.

  • Navab, M., Reddy, S. T., Van Lenten, B. J. and Fogelman, A. M., HDL and cardiovascular disease: atherogenic and atheroprotective mechanisms. Nature Rev. Cardiol., 2011, 8, 222-232; doi:10.1038/nrcardio.2010.222.

  • Bergt, C. et al., The myeloperoxidase product hypochlorous acid oxidizes HDL in the human artery wall and impairs ABCA1dependent cholesterol transport. Proc. Natl. Acad. Sci. USA, 2004, 101(35), 13032-13037. PubMed PMID: 15326314.

  • DiDonato, J. A. et al., Site-specific nitration of apolipoprotein AI at tyrosine 166 is both abundant within human atherosclerotic plaque and dysfunctional. J. Biol. Chem., 2014, 289(15), 10276-10292.

  • Huang, Y. et al., An abundant dysfunctional apolipoprotein A1 in human atheroma. Nature Med., 2014, 20(2), 193-203.

  • Ali, M. et al., Myeloperoxidase inhibition improves ventricular function and remodelling after experimental myocardial infarction. JACC Basic Transl. Sci., 2016, 1(7), 633-643; https://doi.org/10.1016/j.jacbts.2016.09.004.

  • Brennan, M. L. et al., Increased atherosclerosis in myeloperoxidasedeficient mice. J. Clin. Invest., 2001, 107(4), 419-430. PubMed PMID: 11181641.

  • McMillen, T. S., Heinecke, J. W. and LeBoeuf, R. C., Expression of human myeloperoxidase by macrophages promotes atherosclerosis in mice. Circulation, 2005, 111(21), 2798-2804.

  • Castellani, L. W., Chang, J. J., Wang, X., Lusis, A. J. and Reynolds, W. F., Transgenic mice express human MPO-463G/A alleles at atherosclerotic lesions, developing hyperlipidemia and obesity in -463G males. J. Lipid Res., 2006, 47(7), 1366-1377. PubMed PMID: 16639078.

  • Jia, G., Hill, M. A. and Sowers, J. R., Diabetic cardiomyopathy: an update of mechanisms contributing to this clinical entity. Circ. Res., 2018, 122(4), 624-638.

  • Bugger, H. and Abel, E. D., Molecular mechanisms of diabetic cardiomyopathy. Diabetologia, 2014, 57(4), 660-671.

  • Global Report on Diabetes by World Health Organization. Publications by the World Health Organization, 2016, pp. 1-88.

  • Arundgovind, G., Kamalanathan, A. S. and Venkataraman, K., Atherogenic dyslipoprotenemia in type 2 diabetes. In Mechanisms o f Vascular Defects in Diabetes Mellitus (eds Kartha, C. C., Ramachandran, S. and Pillai, R. M.), Advances in Biochemistry in Health and Diseases, Springer Press, Cham, 2017, pp. 451-467.

  • Hasanally, D., Edel, A., Chaudhary, R. and Ravandi, A., Identification of oxidized phosphatidylinositols present in OxLDL and human atherosclerotic plaque. Lipids, 2017, 52(1), 11-26; doi: 10.1007/s11745-016-4217-y.

  • Iqbal, J., Walsh, M. T., Hammad, S. M. and Hussain, M. M., Sphingolipids and lipoproteins in health and metabolic disorders. Trends Endocrinol. Metab., 2017, 28(7), 506-518.

  • Levkau, B., HDL-S1P: cardiovascular functions, disease-associated alterations, and therapeutic applications. Front. Pharmacol., 2015, 6, 243.

  • Saini-Chohan, H. K., Mitchell, R. W., Vaz, F. M., Zelinski, T. and Hatch, G. M., Delineating the role of alterations in lipid metabolism to the pathogenesis of inherited skeletal and cardiac muscle disorders: thematic review series: genetics of human lipid diseases. J. Lipid Res., 2012, 53(1), 4-27.

  • Platt, F. M., Sphingolipid lysosomal storage disorders. Nature, 2014, 510(7503), 68-75.

  • Feitosa, M. F. et al., Genetic analysis of long-lived families reveals novel variants influencing high density-lipoprotein cholesterol. Front. Genet, 2014, 5, 159; doi:10.3389/fgene.2014.00159.

  • Brennan, M.-L. et al., Prognostic value of myeloperoxidase in patients with chest pain. N. Engl. J. Med., 2003, 349, 1595-1604 [PubMed:14573731].

  • Zhang, R. et a l., Association between myeloperoxidase levels and risk of coronary artery disease. J. Am. Med. Assoc., 2001, 286, 2136-2142. PubMed: 11694155.

  • Zheng, L. et al., Apolipoprotein A-I is a selective target for myeloperoxidasecatalyzed oxidation and functional impairment in subjects with cardiovascular disease. J. Clin. Invest., 2004, 114, 529-541. PubMed: 15314690.

  • Rosenson, R. S., et al., Dysfunctional HDL and atherosclerotic cardiovascular disease. Nature Rev. Cardiol., 2016, 13(1), 48-60.

  • Lokeshwaran, K. and Venkataraman, K., Development of monoclonal antibody against chlorinated 192tyrosine containing ApoAI peptide to screen quality of human high density lipoprotein (HDL). Protein Pept. Lett., 2016, 23(10), 905-912. PubMed PMID: 27468813.

  • Zheng, L., Settle, M., Brubaker, G., Schmitt, D., Hazen, S. L., Smith, J. D. and Kinter, M., Localization of nitration and chlorination sites on apolipoprotein A-I catalyzed by myeloperoxidase in human atheroma and associated oxidative impairment in ABCA1-dependent cholesterol efflux from macrophages. J. Biol. Chem., 2005, 280(1), 38-47.

  • Shao, B. et al., Myeloperoxidase impairs ABCA1-dependent cholesterol efflux through methionine oxidation and site-specific tyrosine chlorination of apolipoprotein A-I. J. Biol. Chem., 2006, 281(14), 9001-9004.

  • Shao, B., Oda, M. N., Oram, J. F. and Heinecke, J. W., Myeloperoxidase: an oxidative pathway for generating dysfunctional high-density lipoprotein. Chem. Res. Toxicol., 2010, 23(3), 447^54.

  • Smith, J. D., Dysfunctional HDL as a diagnostic and therapeutic target. Arterioscler. Thromb. Vasc. Biol., 2010, 30(2), 151-155.

  • Holzer, M. et al., Myeloperoxidase-derived chlorinating species induce protein carbamylation through decomposition of thiocyanate and urea: novel pathways generating dysfunctional high-density lipoprotein. Antioxid. Redox Signal., 2012, 17(8), 1043-1052.


Abstract Views: 325

PDF Views: 119




  • Oxidized Lipoproteins as the Diagnostic Target for Cardiovascular Diseases

Abstract Views: 325  |  PDF Views: 119

Authors

S. Sreeja
Pushpagiri Research Centre, Pushpagiri Institute of Medical Sciences and Research Centre, Thiruvalla 689 101, India
Anand Manoharan
The CHILDS Trust Medical Research Foundation, Chennai 600 034, India
Krishnan Venkataraman
Centre for Bio-separation Technology, VIT University, Vellore 632 014, India

Abstract


Low HDL-cholesterol and high LDL-cholesterol in plasma have long been associated with cardiovascular disease (CVD) risk. The quantity of cholesterol associated with these lipoproteins is being traditionally used to predict CVD risk. However, recent studies have suggested that the quality and functionality of these lipoproteins are more important. The lipoproteins - HDL and LDL - undergo both enzymatic and non-enzymatic modifications which impair their functional capability and hence, test of such modification which reflects the quality of HDL can be a good predictor of CVD risk. The present article discusses oxidation- associated dysfunctionality of lipoproteins and their potential in laboratory diagnosis of CVD.

Keywords


Cardiovascular Disease, Cholesterol, Diagnostic Target, Oxidized Lipoproteins.

References





DOI: https://doi.org/10.18520/cs%2Fv115%2Fi7%2F1276-1286