Role of Oxidized Low-density Lipoprotein in Human Diseases: A Review

Journal of Chemical Health Risks

مقاله 8، دوره 11، Special Issue: Bioactive Compounds: Their Role in the Prevention and Treatment of Diseases، دی 2021، صفحه 71-83   

نوع مقاله: Review Article

شناسه دیجیتال (DOI): 10.22034/jchr.2021.684227

نویسندگان

Israa Qusay Falih^{* 1}؛ Mohammed A.H. Alobeady²؛ Shaima Rabeea Banoon³؛ Mohanad Yakdhan Saleh²

¹Department of Chemistry, College of Science, University of Misan, Maysan, Iraq

²Department of Chemistry, College of Education for Pure Science, University of Mosul, Mosul, Iraq

³Department of Biology, College of Science, University of Misan, Maysan, Iraq

چکیده

The current study aims to know the role of low-density lipoprotein (LDL-C) on several variables, as well as its role in diagnosing some diseases by observing its metabolism processes in many diseases affecting humans and the imbalance, is significant in the level of this lipoprotein, which constitutes an essential factor of Risk factors for developing many diseases, especially cardiovascular disease. The present study aims at assessing the oxidized LDL role in pathogenesis.

کلیدواژه‌ها

Oxidized LDL؛ Blood pressure؛ Renal failure؛ Polycystic ovary syndrome؛ Fatty liver

مراجع

1. Parthasarathy  S.,  Raghavamenon A.,  Garelnabi M.O., Santanam N., 2010. Oxidized low-density lipoprotein. Free Radicals and Antioxidant Protocols. 403-417.

2. Volobueva  A.,  Zhang D.,  Grechko A.V., Orekhov A.N., 2018. Foam cell formation and cholesterol trafficking and metabolism disturbances in atherosclerosis. Cor et Vasa.   (in press), 1-7.

3. Sieve I.,  Münster-Kühnel  A.K., Hilfiker-Kleiner D., 2018. Regulation and function of endothelial glycocalyx layer in vascular diseases. Vascular Pharmacology. 100, 26-33.

4. Schlüter  K.D.,  Wolf A.,  Weber M.,  Schreckenberg R., Schulz R., 2017. Oxidized low-density lipoprotein (oxLDL) affects load-free cell shortening of cardiomyocytes in a proprotein convertase subtilisin/kexin 9 (PCSK9)-dependent way. Basic Research in Cardiology, 112 (6), 1-11.

5. Tsimikas  S., 2006. Oxidized low-density lipoprotein biomarkers in atherosclerosis. Current Atherosclerosis Reports. 8(1), 55-61.

6. Steinbrecher U., 1987. Oxidation of human low density lipoprotein results in derivatization of lysine residues of apolipoprotein B by lipid peroxide decomposition products. Journal of Biological Chemistry. 262(8), 3603-3608.

7. Lara-Guzmán O.J.,  Gil-Izquierdo Á.;  Medina S.,  Osorio E.,  Álvarez-Quintero R.,  Zuluaga N.,  Oger C.,  Galano J.M., Durand T., Muñoz-Durango K., 2018. Oxidized LDL triggers changes in oxidative stress and inflammatory biomarkers in human macrophages. Redox Biology. 15, 1-11.

8. Kuksis A., Pruzanski W., 2017. Hydrolysis of Phosphatidylcholine-Isoprostanes (PtdCho-IP) by Peripheral Human Group IIA, V and X Secretory Phospholipases A 2 (sPLA 2). Lipids. 52(6), 477-488.

9. Gdula-Argasińska J.,  Czepiel J., Totoń-Żurańska J.,  Wołkow P.,  Librowski T.,  Czapkiewicz A.,  Perucki W.,  Woźniakiewicz M., Woźniakiewicz A., 2016. n-3 Fatty acids regulate the inflammatory-state related genes in the lung epithelial cells exposed to polycyclic aromatic hydrocarbons. Pharmacological Reports. 68(2), 319-328.

10. Dmitry B.,  Juhaszova  M., Sollot S., 2014. Mitochondrial ROS-induced ROS release: an update and review. Physiol Rev. 94, 909-50.

11. Lin F.Y., Tsao N.W.,  Shih C.M., Lin Y.W., Yeh J.S., Chen J.W., Nakagami H.; Morishita R., Sawamura T., Huang C.Y., 2015. The biphasic effects of oxidized-low density lipoprotein on the vasculogenic function of endothelial progenitor cells. PLoS One. 10(5), 1-17.

12. Tsimikas S.,  Bergmark C., Beyer R.W.,  Patel R., Pattison J., Miller E., Juliano J., Witztum J.L., 2003. Temporal increases in plasma markers of oxidized low-density lipoprotein strongly reflect the presence of acute coronary syndromes. Journal of the American College of Cardiology. 41(3), 360-370.

13. Dong L.F.,  Jameson V.J.,  Tilly D.,  Cerny J.,  Mahdavian E., Marín-Hernández A., Hernández-Esquivel L.,  Rodríguez-Enríquez S.,  Stursa J., Witting P.K., 2011. Mitochondrial targeting of vitamin E succinate enhances its pro-apoptotic and anti-cancer activity via mitochondrial complex II. Journal of Biological Chemistry. 286(5), 3717-3728.

14. Gao S., Liu J., 2017. Association between circulating oxidized low-density lipoprotein and atherosclerotic cardiovascular disease. Chronic Diseases and Translational Medicine. 3(2), 89-94.

15. Leiva E.,  Wehinger S.,  Guzmán L., Orrego R., 2015. Role of oxidized LDL in atherosclerosis. Hypercholesterolemia. 55-78.

16. Uppal N., Uppal V.; Uppal P., 2014. Progression of coronary artery disease (CAD) from stable angina (SA) towards myocardial infarction (MI): role of oxidative stress. Journal of clinical and diagnostic research: JCDR. 8(2), 40-43.

17. Uttara B.,  Singh A.V.,  Zamboni P., Mahajan R., 2009. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Current Neuropharmacology. 7(1), 65-74.

18. Virmani A., Gaetani F., Imam S., 2003. Neuroprotective Effects of L-Carnitine on Methamphetamine-Evoked Neurotoxicity. Ann NY Acad. Sci. 993, 197-207.

19. Xu T.,  Ding W.,  Ji X.,  Ao X.,  Liu Y.,  Yu W., Wang J., 2019. Oxidative stress in cell death and cardiovascular diseases. Oxidative Medicine and Cellular Longevity. Spescial Issue, 1-11.

20. Sagor M.,  Taher A.,  Tabassum N.,  Potol M., Alam M., 2015. Xanthine oxidase inhibitor, allopurinol, prevented oxidative stress, fibrosis, and myocardial damage in isoproterenol induced aged rats. Oxidative Medicine and Cellular longevity. 478039, 1-9.

21. Kregel K.C., Zhang H.J., 2007. An integrated view of oxidative stress in aging: basic mechanisms, functional effects, and pathological considerations. American Journal of Physiology-Regulatory. Integrative and Comparative Physiology. 292(1), 18-36.

22. Parthasarathy S., Wieland E., Steinberg D., 1989. A role for endothelial cell lipoxygenase in the oxidative modification of low density lipoprotein. Proceedings of the National Academy of Sciences. 86(3), 1046-1050.

23. Singh R.,  Devi S., Gollen R., 2015. Role of free radical in atherosclerosis, diabetes and dyslipidaemia: larger‐than‐life. Diabetes/Metabolism Research and Reviews. 31(2), 113-126.

24. Montezano A.C.; Touyz R.M., 2012. Reactive oxygen species and endothelial function–role of nitric oxide synthase uncoupling and Nox family nicotinamide adenine dinucleotide phosphate oxidases. Basic & Clinical Pharmacology & Toxicology. 110(1), 87-94.

25. Meraviglia M.V.,  Maggi E.,  Bellomo G.,  Cursi M.,  Fanelli G., Minicucci F., 2002. Autoantibodies against oxidatively modified lipoproteins and progression of carotid restenosis after carotid endarterectomy. Stroke. 33(4), 1139-1141.

26. Yoshida H., Kisugi R., 2010. Mechanisms of LDL oxidation. Clinica Chimica Acta. 411(23-24), 1875-1882.

27. Strasak A., Rapp K.,  Hilbe W., Oberaigner W.,  Ruttmann E.,  Concin H.,  Diem G.,  Pfeiffer K.,  Ulmer H., VHM; Group, P. S., 2007. The role of serum uric acid as an antioxidant protecting against cancer: prospective study in more than 28000 older Austrian women. Annals of Oncology. 18(11), 1893-1897.

28. Biscione F., Pignalberi C., Totteri A., Messina F., Altamura G., 2007. Cardiovascular effects of omega-3 free fatty acids. Current Vascular Pharmacology. 5(2), 163-172.

29. Calder P.C.,  Dangour A., Diekman C., Eilander A., Koletzko B., Meijer G.,  Mozaffarian D.,  Niinikoski H.,  Osendarp S.J., Pietinen P., 2010. Essential fats for future health. Proceedings of the 9 th Unilever Nutrition Symposium, 26–27 May 2010. European Journal of Clinical Nutrition. 64(4), S1-S13.

30. Mozaffarian D.,  Benjamin E.J.,  Go A.S.,  Arnett D.K., Blaha M.J., Cushman M., De Ferranti S., Després J.P.;  Fullerton H.J., Howard V.J., 2015. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Circulation. 131(4), e29-e322.

31. Itabe H., 2009. Oxidative modification of LDL: its pathological role in atherosclerosis. Clinical Reviews in Allergy & Immunology. 37(1), 4-11.

32. Christensen J.J., Osnes L.T., Halvorsen B.,  Retterstøl K.,  Bogsrud M.P., Wium C., Svilaas A., Narverud I., Ulven S.M., Aukrust P., 2017. Altered leukocyte distribution under hypercholesterolemia: A cross-sectional study in children with familial hypercholesterolemia. Atherosclerosis. 256, 67-74.

33. Robbins C.S.,  Hilgendorf I.,  Weber G.F., Theurl I.,  Iwamoto Y.,  Figueiredo J.L., Gorbatov R., Sukhova G.K.,  Gerhardt L.M., Smyth D., 2013. Local proliferation dominates lesional macrophage accumulation in atherosclerosis. Nature Medicine. 19(9), 1166-1172.

34. Buchert J., Selinheimo E., Kruus K., Mattinen M.L.,  Lantto R., Autio K., 2007. Using crosslinking enzymes to improve textural and other properties of food. In Novel Enzyme Technology for Food Applications, Elsevier. pp 101-139.

35. Matheis G., Whitaker J.R., 1987. A review: enzymatic cross‐linking of proteins applicable to foods. Journal of Food Biochemistry. 11(4), 309-327.

36. Takahashi Y.,  Zhu H., Yoshimoto T., 2005. Essential roles of lipoxygenases in LDL oxidation and development of atherosclerosis. Antioxidants & Redox Signaling. 7(3-4), 425-431.

37. Andreou A., Feussner I., 2009. Lipoxygenases–structure and reaction mechanism. Phytochemistry. 70(13-14), 1504-1510.

38. Gebauer S.K.,  Psota T.L.,  Harris W.S., Kris-Etherton P.M., 2006. n− 3 fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits. The American Journal of Clinical Nutrition. 83(6), 1526S-1535S.

39. Cook H.W., McMaster C.R., 2002. Fatty acid desaturation and chain elongation in eukaryotes. In New Comprehensive Biochemistry, Elsevier. 36, 181-204.

40. Klebanoff S.J., 2005. Myeloperoxidase: friend and foe. Journal of Leukocyte Biology. 77(5), 598-625.

41. Schindhelm R.K., van der Zwan L.P., Teerlink T., Scheffer P.G., 2009. Myeloperoxidase: a useful biomarker for cardiovascular disease risk stratification? Clinical Chemistry. 55(8), 1462-1470.

42. Krauss R.M., 2004. Lipids and lipoproteins in patients with type 2 diabetes. Diabetes Care. 27(6), 1496-1504.

43. Torzewski M., Suriyaphol P., Paprotka K., Spath L., Ochsenhirt V., Schmitt A., Han S.R., Husmann M., Gerl V.B., Bhakdi S., 2004. Enzymatic modification of low-density lipoprotein in the arterial wall: a new role for plasmin and matrix metalloproteinases in atherogenesis. Arteriosclerosis, Thrombosis and Vascular Biology. 24(11), 2130-2136.

44. Stocker R., Keaney Jr.J.F., 2004. Role of oxidative modifications in atherosclerosis. Physiological Reviews. 84(4), 1381-1478.

45. Herrero A., Portero-Otı́n M., Bellmunt M.A.J., Pamplona R., Barja G., 2001. Effect of the degree of fatty acid unsaturation of rat heart mitochondria on their rates of H₂O₂ production and lipid and protein oxidative damage. Mechanisms of Ageing and Development. 122(4), 427-443.

46. Nicholls S.J., Hazen S.L., 2009. Myeloperoxidase, modified lipoproteins, and atherogenesis. Journal of Lipid Research. 50, S346-S351.

47. Chisvert A., Salvador A. eds., 2007. Analysis of cosmetic products. Elsevier. 1^st ed. p. 506.

48. Vivó-Sesé I., Pla M., 2007. Bioactive Ingredients in Cosmetics. Analysis of Cosmetic Products. 380-389.

49. Sanguinetti S.M., Schreier L.E., Elbert A., Fasulo V., Ferrari N., Wikinski R.L., 1999. Detection of structural alterations in LDL isolated from type 2 diabetic patients: application of the fructosamine assay to evaluate the extent of LDL glycation. Atherosclerosis. 143(1), 213-215.

50. Tames F.J.,  Mackness M.I.,  Arrol S.,  Laing I., Durrington P.N., 1992. Non-enzymatic glycation of apolipoprotein B in the sera of diabetic and non-diabetic subjects. Atherosclerosis. 93(3), 237-244.

51. Yoshida H., Ishikawa T., Nakamura H., 1997. Vitamin E/Lipid Peroxide Ratio and Susceptibility of LDL to Oxidative Modification in Non–Insulin-Dependent Diabetes Mellitus. Arteriosclerosis, Thrombosis, and Vascular Biology. 17(7), 1438-1446.

52. Kawamura M., Heinecke J.W., Chait A., 1994. Pathophysiological concentrations of glucose promote oxidative modification of low density lipoprotein by a superoxide-dependent pathway. The Journal of Clinical Investigation. 94(2), 771-778.

53. Kurutas E.B., 2015. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutrition Journal. 15(1), 1-22.

54. Is  Y., Woodside J., 2001. Antioxidant in health and disease. J Clin Pathol. 54(3), 176-186.

55. Montuschi P., Barnes P.J., Roberts L.J., 2004. Isoprostanes: markers and mediators of oxidative stress. The FASEB Journal. 18(15), 1791-1800.

56. Khosravi M., Poursaleh A., Ghasempour G., Farhad S., Najafi M., 2019. The effects of oxidative stress on the development of atherosclerosis. Biological Chemistry. 400(6), 711-732.

57. Wagner A.H., Kautz O., Fricke K., Zerr-Fouineau M., Demicheva E., Guldenzoph B.R.,  ermejo J.L., Korff T., Hecker M., 2009. Upregulation of glutathione peroxidase offsets stretch-induced proatherogenic gene expression in human endothelial cells. Arteriosclerosis, Thrombosis, and Vascular Biology. 29(11), 1894-1901.

58. Santos-Sánchez N.F., Salas-Coronado R., Villanueva-Cañongo C., Hernández-Carlos B., 2019. Antioxidant compounds and their antioxidant mechanism. IntechOpen. London, UK. pp. 1-28.

59. Steinberg D., 1997. Low density lipoprotein oxidation and its pathobiological significance. Journal of Biological Chemistry. 272(34), 20963-20966.

60. Ceriello A., 2008. Possible role of oxidative stress in the pathogenesis of hypertension. Diabetes Care. 31(Supplement 2), 181-184.

61. Guxens M., Fitó M., Martínez-González M.A., Salas-Salvadó J., Estruch R., Vinyoles E., Fiol M., Corella D., Arós F., Gómez-Gracia E., 2009. Hypertensive status and lipoprotein oxidation in an elderly population at high cardiovascular risk. American Journal of Hypertension. 22(1), 68-73.

62. Ross R., 1999. Atherosclerosis—an inflammatory disease. New England Journal of Medicine. 340(2), 115-126.

63. Wang A., Li S., Zhang N., Dai L., Zuo Y., Wang Y., Meng X.,Wang Y., 2018. Oxidized low-density lipoprotein to high-density lipoprotein ratio predicts recurrent stroke in minor stroke or transient ischemic attack. Stroke. 49(11), 2637-2642.

64. Koenig W., 1999. Atherosclerosis involves more than just lipids: focus on inflammation. European Heart Journal Supplements. 1(T), T19-T26.

65. Witztum J.L., 1997. Role of modified lipoproteins in diabetic macroangiopathy. Diabetes. 46 (Supplement 2), 112-114.

66. Holvoet P.,  Stassen J.M., Van Cleemput J., Collen D.S., Vanhaecke J., 1998. Oxidized low density lipoproteins in patients with transplant-associated coronary artery disease. Arteriosclerosis, Thrombosis, and Vascular Biology. 18(1), 100-107.

67. Steinberg D., 1989. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl j Med. 320, 915-924.

68. Toshima S.I.  Hasegawa A., Kurabayashi M., Itabe H.,  Takano T.,  Sugano J.,  Shimamura K.,  Kimura J., Michishita I., Suzuki T., 2000. Circulating oxidized low density lipoprotein levels: a biochemical risk marker for coronary heart disease. Arteriosclerosis, Thrombosis, and Vascular Biology. 20(10), 2243-2247.

69. Steinberg D., 1997. Lewis A. Conner Memorial Lecture: oxidative modification of LDL and atherogenesis. Circulation. 95(4), 1062-1071.

70. Barbieri S.S., Cavalca V., Eligini S., Brambilla M., Caiani A., Tremoli E., Colli S., 2004. Apocynin prevents cyclooxygenase 2 expression in human monocytes through NADPH oxidase and glutathione redox-dependent mechanisms. Free Radical Biology and Medicine. 37(2), 156-165.

71. Niimi M., Keyamura Y.,  Nozako M.,  Koyama T.,  Kohashi M., Yasufuku R., Yoshikawa T., Fan J., 2013. Probucol inhibits the initiation of atherosclerosis in cholesterol-fed rabbits. Lipids in Health and Disease. 12(1), 1-8.

72. De Meyer G.R., Kockx M.M., Knaapen M.W., Martinet W., De Cleen D.M., Bult H., Herman A.G., 2003. Nitric oxide donor molsidomine favors features of atherosclerotic plaque stability during cholesterol lowering in rabbits. Journal of Cardiovascular Pharmacology. 41(6), 970-978.

73. Witztum J.L., 1993. Role of oxidised low density lipoprotein in atherogenesis. British Heart Journal. 69(1 Suppl), 12-18.

74. Davidson M.H., Toth P.P., 2007. High-density lipoprotein metabolism: potential therapeutic targets. The American Journal of Cardiology. 100(11), S32-S40.

75. Inoue T., Uchida T., Kamishirado H., Takayanagi K., Morooka S., 2001. Antibody against oxidized low density lipoprotein may predict progression or regression of atherosclerotic coronary artery disease. Journal of the American College of Cardiology. 37(7), 1871-1876.

76.    Aviram, M., 2000. Review of human studies on oxidative damage and antioxidant protection related to cardiovascular diseases. Free Radical Research 33, S85-97.

77. Watson A.D.,  Berliner J.A.,  Hama S.Y., La Du B.N., Faull K.F., Fogelman A.M., Navab M., 1995. Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. The Journal of Clinical Investigation. 96(6), 2882-2891.

78. Moradi H., Pahl M.V., Elahimehr R., Vaziri N.D., 2009. Impaired antioxidant activity of high-density lipoprotein in chronic kidney disease. Translational Research. 153(2), 77-85.

79. Karimi S.,  Dadvar M., Modarress H., Dabir B., 2013. Kinetic modeling of low density lipoprotein oxidation in arterial wall and its application in atherosclerotic lesions prediction. Chemistry and Physics of Lipids. 175, 1-8.

80. Holvoet P., Vanhaecke J., Janssens S., Van de Werf F., Collen D., 1998. Oxidized LDL and malondialdehyde-modified LDL in patients with acute coronary syndromes and stable coronary artery disease. Circulation. 98(15), 1487-1494.

81. Ampuero J.,  Ranchal I.,  Gallego‐Durán R.,  Pareja M.J.,  Del Campo J.A.,  Pastor‐Ramírez H.,  Rico M.C.,  Picón R.,  Pastor L., García‐Monzón C., 2016. Oxidized low‐density lipoprotein antibodies/high‐density lipoprotein cholesterol ratio is linked to advanced non‐alcoholic fatty liver disease lean patients. Journal of Gastroenterology and Hepatology. 31(9), 1611-1618.

82. Lori Mosca M., Rubenfire M., Tarshis T., Thomas Pearson M., 1997. Clinical predictors of oxidized low-density lipoprotein in patients with coronary artery disease. The American Journal of Cardiology. 80(7), 825-830.

83. Cotter T.G., Rinella M., 2020. Nonalcoholic fatty liver disease 2020: the state of the disease. Gastroenterology. 158(7), 1851-1864.

84. Holvoet P., Mertens A., Verhamme P., Bogaerts K., Beyens G., Verhaeghe R., Collen D., Muls E., Van de Werf F., 2001. Circulating oxidized LDL is a useful marker for identifying patients with coronary artery disease. Arteriosclerosis, Thrombosis, and Vascular Biology. 21(5), 844-848.

85. Busch C.J., Binder C.J., 2017. Malondialdehyde epitopes as mediators of sterile inflammation. Biochimica et Biophysica Acta (BBA)-Molecular and Cell Biology of Lipids. 1862(4), 398-406.

86. Gritti B.B., Binder C.J., 2016. Oxidation-specific epitopes are major targets of innate immunity in atherothrombosis. Hämostaseologie. 36(2), 89-96.

87. Leibundgut G., Witztum J.L., Tsimikas S., 2013. Oxidation-specific epitopes and immunological responses: Translational biotheranostic implications for atherosclerosis. Current Opinion in Pharmacology. 13(2), 168-179.

88. Papac-Milicevic N., Busch C.L., Binder C.J., 2016. Malondialdehyde epitopes as targets of immunity and the implications for atherosclerosis. Advances in Immunology. 131, 1-59.

89. Binder C.J., Papac-Milicevic N., Witztum J.L., 2016. Innate sensing of oxidation-specific epitopes in health and disease. Nature Reviews Immunology. 16(8), 485-497.

90. Kaplan M., Aviram M., 1999. Oxidized low density lipoprotein: atherogenic and proinflammatory characteristics during macrophage foam cell formation. An Inhibitory role for nutritional antioxidants and serum paraoxonase. Clin Chem Lab Med. 37(8), 777-787.

91.    Murray C.J., Lopez A.D., 1997. Mortality by cause for eight regions of the world: Global Burden of Disease Study. The Lancet. 349(9061), 1269-1276.

92. Uno M.,  Kitazato K.,  Nishi K.,  Itabe H., Nagahiro S., 2003. Raised plasma oxidised LDL in acute cerebral infarction. Journal of Neurology, Neurosurgery & Psychiatry. 74(3), 312-316.

93. Aviram M., Rosenblat M., Etzioni A., Levy R., 1996. Activation of NADPH oxidase is required for macrophage-mediated oxidation of low-density lipoprotein. Metabolism. 45(9), 1069-1079.

94. Mohammed A.H., Jasim S.Z.J., 2020. Effect of Blood Pressure on the lipids and Percentage of Fatty Acids of Blood Serum. International Journal of Psychosocial Rehabilitation. 24(7), 2688-2694.

95. Murray C.J., Lopez A.D., 1997. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. The Lancet. 349(9063), 1436-1442.

96. Hendrikx T., Binder C.J., 2020. Oxidation-specific epitopes in non-alcoholic fatty liver disease. Frontiers in Endocrinology. 11, 1-10.

97. Babakr A.T.,  Elsheikh O.M.,  Almarzouki A.A., Assiri A.M., Abdalla B.E.E.,  Zaki H.Y.,  Fatani S.H., NourEldin E.M., 2014. Relationship between oxidized low-density lipoprotein antibodies and obesity in different glycemic situations. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. 7, 513-520.

98. Schreurs M.P., Cipolla M.J., 2014. Cerebrovascular dysfunction and blood-brain barrier permeability induced by oxidized LDL are prevented by apocynin and magnesium sulfate in female rats. Journal of Cardiovascular Pharmacology. 63(1), 33-39.

99. Nakhjavani M., Khalilzadeh O., Khajeali L.,  Esteghamati A., Morteza A., Jamali A., Dadkhahipour S., 2010. Serum oxidized‐LDL is associated with diabetes duration independent of maintaining optimized levels of LDL‐cholesterol. Lipids. 45(4), 321-327.

100. Gutwein P., Abdel‐Bakky M.S., Doberstein K., Schramme A., Beckmann J., Schaefer L., Amann K., Doller A.,  Kämpfer‐Kolb N., Abdel‐Aziz A.A.H., 2009. CXCL16 and oxLDL are induced in the onset of diabetic nephropathy. Journal of Cellular and Molecular Medicine. 13(9b), 3809-3825.

101. Mshelia D., Pindiga H., 2004. Dyslipidaemia, Lipid Oxidation, And Free Radicals In Diabetic Nephropathy: An Overview. Highland Medical Research Journal. 2(1), 1-7.

102. Nomura S.,  Shouzu A.,  Omoto S., Nishikawa M., Iwasaka T., Fukuhara S., 2004. Activated platelet and oxidized LDL induce endothelial membrane vesiculation: clinical significance of endothelial cell-derived microparticles in patients with type 2 diabetes. Clinical and Applied Thrombosis/Hemostasis. 10(3), 205-215.

103. Abdelsamie S.A., Li Y., Huang Y., Lee M.H., Klein R.L., Virella G., Lopes-Virella M.F., 2011. Oxidized LDL immune complexes stimulate collagen IV production in mesangial cells via Fc gamma receptors I and III. Clinical Immunology. 139(3), 258-266.

104. Kopprasch S., Pietzsch J., Kuhlisch E., Fuecker K., Temelkova-Kurktschiev T.,  Hanefeld M.,  Kühne H.,  Julius U., Graessler J., 2002. In vivo evidence for increased oxidation of circulating LDL in impaired glucose tolerance. Diabetes. 51(10), 3102-3106.

105. Wu Y., Tang L., Chen B., 2014. Oxidative stress: implications for the development of diabetic retinopathy and antioxidant therapeutic perspectives. Oxidative Medicine and Cellular Longevity. 2014(752387), 1-12.

106. Jeremy Y.Y., Lyons T.J., 2013. Modified lipoproteins in diabetic retinopathy: a local action in the retina. Journal of Clinical & Experimental Ophthalmology. 4(6), 1-17.

107. Vrieling F., Wilson L., Rensen P.C., Walzl G.,  Ottenhoff T.H., Joosten S.A., 2019. Oxidized low-density lipoprotein (oxLDL) supports Mycobacterium tuberculosis survival in macrophages by inducing lysosomal dysfunction. PLoS Pathogens. 15(4), 1-27.

108. Ganjifrockwala F., Joseph J., George G., 2016. Serum oxidized LDL levels in type 2 diabetic patients with retinopathy in Mthatha Region of the Eastern Cape Province of South Africa. Oxidative Medicine and Cellular Longevity. 2063103, 1-8.

109. Jeon C.Y., Murray M.B., 2008. Diabetes mellitus increases the risk of active tuberculosis: a systematic review of 13 observational studies. PLoS Medicine. 5(7), 1091-1101.

110. Lawi Z.K.K., Merza F.A., Banoon S.R., Al-Saady M.A.A.J., Al-Abboodi A., 2021. Mechanisms of Antioxidant Actions and their Role in many Human Diseases: A Review. Journal of Chemical Health Risks. 11(Special Issue), 45-57.