Home LiteratureArticle Details
PMID: 24251116 Published · epublish English Journal Article Review

Biological markers of oxidative stress: Applications to cardiovascular research and practice.

Redox biology ·Vol. 1 ·2013-10-08 ·Pages 483-91

Ho E, Karimi Galougahi K, Liu CC, Bhindi R, Figtree GA

Abstract

Oxidative stress is a common mediator in pathogenicity of established cardiovascular risk factors. Furthermore, it likely mediates effects of emerging, less well-defined variables that contribute to residual risk not explained by traditional factors. Functional oxidative modifications of cellular proteins, both reversible and irreversible, are a causal step in cellular dysfunction. Identifying markers of oxidative stress has been the focus of many researchers as they have the potential to act as an "integrator" of a multitude of processes that drive cardiovascular pathobiology. One of the major challenges is the accurate quantification of reactive oxygen species with very short half-life. Redox-sensitive proteins with important cellular functions are confined to signalling microdomains in cardiovascular cells and are not readily available for quantification. A popular approach is the measurement of stable by-products modified under conditions of oxidative stress that have entered the circulation. However, these may not accurately reflect redox stress at the cell/tissue level. Many of these modifications are "functionally silent". Functional significance of the oxidative modifications enhances their validity as a proposed biological marker of cardiovascular disease, and is the strength of the redox cysteine modifications such as glutathionylation. We review selected biomarkers of oxidative stress that show promise in cardiovascular medicine, as well as new methodologies for high-throughput measurement in research and clinical settings. Although associated with disease severity, further studies are required to examine the utility of the most promising oxidative biomarkers to predict prognosis or response to treatment.

Keywords
Biomarker CVD cardiovascular disease Cardiovascular disease GSH glutathione (reduced) Glutathionylation H2O2 hydrogen peroxide HO2• hydroperoxyl radical HOCl hypochlorous acid IsoP isoprostane MDA malondialdehyde MPO myeloperoxidase NO2 nitrogen dioxide O2•− superoxide ONOO− peroxynitrite OxLDL Oxidized low-density lipoprotein Oxidative stress Prognosis ROS reactive oxygen species TBARS thiobarbituric acid reacting substance •OH hydroxyl radical
MeSH Terms
Animals Biomarkers/metabolism Biomedical Research Cardiovascular Diseases/drug therapy,metabolism Humans Oxidative Stress
Chemicals
Biomarkers
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Ho Edwin
North Shore Heart Research Group, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia.
Karimi Galougahi Keyvan
Liu Chia-Chi
Bhindi Ravi
Figtree Gemma A
References (101)
101 references, click to expand
  1. Quantification of isoprostanes as indices of oxidant stress and the risk of atherosclerosis in humans.
    Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):279-86 PMID: 15591226
  2. NO-dependent protein nitration: a cell signaling event or an oxidative inflammatory response?
    Trends Biochem Sci. 2003 Dec;28(12):646-54 PMID: 14659696
  3. Role of reactive aldehyde in cardiovascular diseases.
    Free Radic Biol Med. 2000 Jun 15;28(12):1685-96 PMID: 10946210
  4. Glutathione and alpha-lipoate in diabetic rats: nerve function, blood flow and oxidative state.
    Eur J Clin Invest. 2001 May;31(5):417-24 PMID: 11380593
  5. Non-cyclooxygenase-derived prostanoids (F2-isoprostanes) are formed in situ on phospholipids.
    Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10721-5 PMID: 1438268
  6. Plasma oxidized low-density lipoprotein, a strong predictor for acute coronary heart disease events in apparently healthy, middle-aged men from the general population.
    Circulation. 2005 Aug 2;112(5):651-7 PMID: 16043640
  7. Glutathionyl hemoglobin in uremic patients undergoing hemodialysis and continuous ambulatory peritoneal dialysis.
    Kidney Int Suppl. 2001 Feb;78:S155-8 PMID: 11169002
  8. Recombinant human superoxide dismutase (h-SOD) fails to improve recovery of ventricular function in patients undergoing coronary angioplasty for acute myocardial infarction.
    Circulation. 1994 May;89(5):1982-91 PMID: 8181121
  9. Protein tyrosine nitration in hydrophilic and hydrophobic environments.
    Amino Acids. 2007;32(4):501-15 PMID: 17077966
  10. Effect of aminoguanidine on erythrocyte lipid peroxidation and activities of antioxidant enzymes in experimental diabetes.
    Clin Chem Lab Med. 1998 Oct;36(10):771-5 PMID: 9853804
  11. A comparison of methods for the measurement of 8-isoPGF(2α): a marker of oxidative stress.
    Ann Clin Biochem. 2011 Mar;48(Pt 2):147-54 PMID: 21292864
  12. 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 May 1;99(9):2075-81 PMID: 9151778
  13. Vitamin E supplementation and cardiovascular events in high-risk patients.
    N Engl J Med. 2000 Jan 20;342(3):154-60 PMID: 10639540
  14. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes.
    Diabetes Care. 2009 Jul;32(7):1327-34 PMID: 19502545
  15. The isoprostanes: unique products of arachidonic acid oxidation-a review.
    Curr Med Chem. 2003 Sep;10(17):1723-40 PMID: 12871112
  16. Prostaglandin F2-like compounds, F2-isoprostanes, are present in increased amounts in human atherosclerotic lesions.
    Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):3236-41 PMID: 9409317
  17. Oxidized forms of glutathione in peripheral blood as biomarkers of oxidative stress.
    Clin Chem. 2006 Jul;52(7):1406-14 PMID: 16690733
  18. β(3) adrenergic stimulation of the cardiac Na+-K+ pump by reversal of an inhibitory oxidative modification.
    Circulation. 2010 Dec 21;122(25):2699-708 PMID: 21135361
  19. Sensitive troponin I assay in early diagnosis of acute myocardial infarction.
    N Engl J Med. 2009 Aug 27;361(9):868-77 PMID: 19710485
  20. The oxidative modification hypothesis of atherogenesis: an overview.
    Free Radic Biol Med. 2000 Jun 15;28(12):1815-26 PMID: 10946223
  21. Assessing the role of circulating, genetic, and imaging biomarkers in cardiovascular risk prediction.
    Circulation. 2011 Feb 8;123(5):551-65 PMID: 21300963
  22. Stability of novel plasma markers associated with cardiovascular disease: processing within 36 hours of specimen collection.
    Clin Chem. 2002 Oct;48(10):1781-4 PMID: 12324497
  23. Increased nitration of sarcoplasmic reticulum Ca2+-ATPase in human heart failure.
    Circulation. 2005 Mar 1;111(8):988-95 PMID: 15710754
  24. Clinical application of C-reactive protein for cardiovascular disease detection and prevention.
    Circulation. 2003 Jan 28;107(3):363-9 PMID: 12551853
  25. Identification of cysteines involved in S-nitrosylation, S-glutathionylation, and oxidation to disulfides in ryanodine receptor type 1.
    J Biol Chem. 2006 Dec 29;281(52):40354-68 PMID: 17071618
  26. S-glutathionylation uncouples eNOS and regulates its cellular and vascular function.
    Nature. 2010 Dec 23;468(7327):1115-8 PMID: 21179168
  27. Tyrosine nitration impairs mammalian aldolase A activity.
    Mol Cell Proteomics. 2004 Jun;3(6):548-57 PMID: 14978198
  28. Correlation between intima-to-media ratio, apolipoprotein B-100, myeloperoxidase, and hypochlorite-oxidized proteins in human atherosclerosis.
    Free Radic Biol Med. 2001 Nov 15;31(10):1254-62 PMID: 11705704
  29. ATVB in focus: redox mechanisms in blood vessels.
    Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):274-8 PMID: 15514203
  30. Biomarkers.
    Mol Aspects Med. 2002 Feb-Jun;23(1-3):101-208 PMID: 12079771
  31. Redox signaling in cardiac physiology and pathology.
    Circ Res. 2012 Sep 28;111(8):1091-106 PMID: 23023511
  32. Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes.
    Circulation. 2003 Sep 23;108(12):1440-5 PMID: 12952835
  33. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.
    N Engl J Med. 2008 Nov 20;359(21):2195-207 PMID: 18997196
  34. Reversible oxidative modification: implications for cardiovascular physiology and pathophysiology.
    Trends Cardiovasc Med. 2010 Apr;20(3):85-90 PMID: 21130951
  35. S-Glutathiolation by peroxynitrite activates SERCA during arterial relaxation by nitric oxide.
    Nat Med. 2004 Nov;10(11):1200-7 PMID: 15489859
  36. Myeloperoxidase: a useful biomarker for cardiovascular disease risk stratification?
    Clin Chem. 2009 Aug;55(8):1462-70 PMID: 19556446
  37. Stability of measurements of biomarkers of oxidative stress in blood over 36 hours.
    Cancer Epidemiol Biomarkers Prev. 2004 Aug;13(8):1399-402 PMID: 15298964
  38. Nitric oxide modulates the catalytic activity of myeloperoxidase.
    J Biol Chem. 2000 Feb 25;275(8):5425-30 PMID: 10681518
  39. Paraoxonase inhibits high-density lipoprotein oxidation and preserves its functions. A possible peroxidative role for paraoxonase.
    J Clin Invest. 1998 Apr 15;101(8):1581-90 PMID: 9541487
  40. Effects of superoxide dismutase on reperfusion arrhythmias and left ventricular function in patients undergoing thrombolysis for anterior wall acute myocardial infarction.
    Am J Cardiol. 1991 Apr 1;67(8):765-7 PMID: 1900979
  41. Short-term gemfibrozil treatment reverses lipid profile and peroxidation but does not alter blood glucose and tissue antioxidant enzymes in chronically diabetic rats.
    Mol Cell Biochem. 2001 Jan;216(1-2):59-63 PMID: 11216864
  42. A causative role for redox cycling of myoglobin and its inhibition by alkalinization in the pathogenesis and treatment of rhabdomyolysis-induced renal failure.
    J Biol Chem. 1998 Nov 27;273(48):31731-7 PMID: 9822635
  43. Oxidative stress and cardiovascular injury: Part I: basic mechanisms and in vivo monitoring of ROS.
    Circulation. 2003 Oct 21;108(16):1912-6 PMID: 14568884
  44. Comparison effect of atorvastatin (10 versus 80 mg) on biomarkers of inflammation and oxidative stress in subjects with metabolic syndrome.
    Am J Cardiol. 2008 Aug 1;102(3):321-5 PMID: 18638594
  45. Serum levels of thiobarbituric acid reactive substances predict cardiovascular events in patients with stable coronary artery disease: a longitudinal analysis of the PREVENT study.
    J Am Coll Cardiol. 2004 Nov 16;44(10):1996-2002 PMID: 15542282
  46. Increased glutathionyl hemoglobin in diabetes mellitus and hyperlipidemia demonstrated by liquid chromatography/electrospray ionization-mass spectrometry.
    Clin Chem. 2000 Jan;46(1):82-8 PMID: 10620575
  47. Association of nitrotyrosine levels with cardiovascular disease and modulation by statin therapy.
    JAMA. 2003 Apr 2;289(13):1675-80 PMID: 12672736
  48. Detection of sequence-specific tyrosine nitration of manganese SOD and SERCA in cardiovascular disease and aging.
    Am J Physiol Heart Circ Physiol. 2006 Jun;290(6):H2220-7 PMID: 16399855
  49. Isoprostanes: markers and mediators of oxidative stress.
    FASEB J. 2004 Dec;18(15):1791-800 PMID: 15576482
  50. S-glutathiolation in life and death decisions of the cell.
    Free Radic Res. 2011 Jan;45(1):3-15 PMID: 20815784
  51. 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 Jul 10;50(2):159-65 PMID: 17616301
  52. 3-Nitrotyrosine modification of SERCA2a in the aging heart: a distinct signature of the cellular redox environment.
    Biochemistry. 2005 Oct 4;44(39):13071-81 PMID: 16185075
  53. Elevated levels of oxidized low density lipoprotein show a positive relationship with the severity of acute coronary syndromes.
    Circulation. 2001 Apr 17;103(15):1955-60 PMID: 11306523
  54. Selective nitration of prostacyclin synthase and defective vasorelaxation in atherosclerotic bovine coronary arteries.
    Am J Pathol. 1999 May;154(5):1359-65 PMID: 10329589
  55. Mechanisms of free radical oxidation of unsaturated lipids.
    Lipids. 1995 Apr;30(4):277-90 PMID: 7609594
  56. Oxidative regulation of the Na(+)-K(+) pump in the cardiovascular system.
    Free Radic Biol Med. 2012 Dec 15;53(12):2263-8 PMID: 23085513
  57. Oxidized low-density lipoprotein biomarkers in atherosclerosis.
    Curr Atheroscler Rep. 2006 Jan;8(1):55-61 PMID: 16455015
  58. Association between cigarette smoking and lipid peroxidation in a controlled feeding study.
    Circulation. 1997 Aug 19;96(4):1097-101 PMID: 9286935
  59. Nrf2-ARE stress response mechanism: a control point in oxidative stress-mediated dysfunctions and chronic inflammatory diseases.
    Free Radic Res. 2010 Nov;44(11):1267-88 PMID: 20815789
  60. Low density lipoprotein oxidation and its pathobiological significance.
    J Biol Chem. 1997 Aug 22;272(34):20963-6 PMID: 9261091
  61. Biochemistry of protein tyrosine nitration in cardiovascular pathology.
    Cardiovasc Res. 2007 Jul 15;75(2):291-302 PMID: 17544386
  62. Peroxynitrite modification of low-density lipoprotein leads to recognition by the macrophage scavenger receptor.
    FEBS Lett. 1993 Sep 13;330(2):181-5 PMID: 8365489
  63. Protein kinase-dependent oxidative regulation of the cardiac Na+-K+ pump: evidence from in vivo and in vitro modulation of cell signalling.
    J Physiol. 2013 Jun 15;591(12):2999-3015 PMID: 23587884
  64. Release of free F2-isoprostanes from esterified phospholipids is catalyzed by intracellular and plasma platelet-activating factor acetylhydrolases.
    J Biol Chem. 2006 Feb 24;281(8):4616-23 PMID: 16371369
  65. Inactivation of tyrosine hydroxylase by nitration following exposure to peroxynitrite and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
    Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7659-63 PMID: 9636206
  66. Reversible oxidative modification: a key mechanism of Na+-K+ pump regulation.
    Circ Res. 2009 Jul 17;105(2):185-93 PMID: 19542013
  67. Human atherosclerotic intima and blood of patients with established coronary artery disease contain high density lipoprotein damaged by reactive nitrogen species.
    J Biol Chem. 2004 Oct 8;279(41):42977-83 PMID: 15292228
  68. Role of oxidative stress in atherosclerosis.
    Am J Cardiol. 2003 Feb 6;91(3A):7A-11A PMID: 12645638
  69. A review of approaches to the analysis of 3-nitrotyrosine.
    Amino Acids. 2003 Dec;25(3-4):351-61 PMID: 14661096
  70. Oxidation of guaiacol by myeloperoxidase: a two-electron-oxidized guaiacol transient species as a mediator of NADPH oxidation.
    Biochem J. 1998 Dec 1;336 ( Pt 2):395-404 PMID: 9820817
  71. Oxidized LDL and malondialdehyde-modified LDL in patients with acute coronary syndromes and stable coronary artery disease.
    Circulation. 1998 Oct 13;98(15):1487-94 PMID: 9769301
  72. Effect of collection tube type and preanalytical handling on myeloperoxidase concentrations.
    Clin Chem. 2008 Jun;54(6):1076-9 PMID: 18509013
  73. Myeloperoxidase, a catalyst for lipoprotein oxidation, is expressed in human atherosclerotic lesions.
    J Clin Invest. 1994 Jul;94(1):437-44 PMID: 8040285
  74. The importance of lipid-derived malondialdehyde in diabetes mellitus.
    Diabetologia. 2000 May;43(5):550-7 PMID: 10855528
  75. Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators.
    Cell. 2006 Oct 20;127(2):397-408 PMID: 17055439
  76. Oxidation of LDL by myeloperoxidase and reactive nitrogen species: reaction pathways and antioxidant protection.
    Arterioscler Thromb Vasc Biol. 2000 Jul;20(7):1716-23 PMID: 10894808
  77. Proteins as biomarkers of oxidative/nitrosative stress in diseases: the contribution of redox proteomics.
    Mass Spectrom Rev. 2005 Jan-Feb;24(1):55-99 PMID: 15389864
  78. The addition of niacin to statin therapy improves high-density lipoprotein cholesterol levels but not metrics of functionality.
    J Am Coll Cardiol. 2013 Nov 12;62(20):1909-10 PMID: 23933538
  79. Angiotensin II type 1 receptor blockers reduce urinary oxidative stress markers in hypertensive diabetic nephropathy.
    Hypertension. 2006 Apr;47(4):699-705 PMID: 16505207
  80. Prognostic value of myeloperoxidase in patients with chest pain.
    N Engl J Med. 2003 Oct 23;349(17):1595-604 PMID: 14573731
  81. Effects of valsartan or amlodipine on endothelial function and oxidative stress after one year follow-up in patients with essential hypertension.
    Clin Exp Hypertens. 2008 Apr;30(3):267-76 PMID: 18425706
  82. Lipoprotein oxidation and progression of carotid atherosclerosis.
    Circulation. 1997 Feb 18;95(4):840-5 PMID: 9054740
  83. Association between myeloperoxidase levels and risk of coronary artery disease.
    JAMA. 2001 Nov 7;286(17):2136-42 PMID: 11694155
  84. Peroxynitrite-mediated inactivation of manganese superoxide dismutase involves nitration and oxidation of critical tyrosine residues.
    Biochemistry. 1998 Feb 10;37(6):1613-22 PMID: 9484232
  85. The potential use of glutathionyl hemoglobin as a clinical marker of oxidative stress.
    Clin Chem. 2000 Feb;46(2):145-6 PMID: 10657367
  86. Alpha-tocopherol supplementation in healthy individuals reduces low-density lipoprotein oxidation but not atherosclerosis: the Vitamin E Atherosclerosis Prevention Study (VEAPS).
    Circulation. 2002 Sep 17;106(12):1453-9 PMID: 12234947
  87. Evaluating oxidative stress in human cardiovascular disease: methodological aspects and considerations.
    Curr Med Chem. 2012;19(16):2504-20 PMID: 22489713
  88. Oxidized LDL and HDL: antagonists in atherothrombosis.
    FASEB J. 2001 Oct;15(12):2073-84 PMID: 11641234
  89. Pro-thrombotic state induced by post-translational modification of fibrinogen by reactive nitrogen species.
    J Biol Chem. 2004 Mar 5;279(10):8820-6 PMID: 14681238
  90. Myeloperoxidase and cardiovascular disease.
    Arterioscler Thromb Vasc Biol. 2005 Jun;25(6):1102-11 PMID: 15790935
  91. Glutathionylation of beta-actin via a cysteinyl sulfenic acid intermediary.
    BMC Biochem. 2007 Dec 10;8:26 PMID: 18070357
  92. Indices of lipid peroxidation in vivo: strengths and limitations.
    Free Radic Biol Med. 2000 Jun 15;28(12):1745-50 PMID: 10946216
  93. Artifact-free quantification of free 3-chlorotyrosine, 3-bromotyrosine, and 3-nitrotyrosine in human plasma by electron capture-negative chemical ionization gas chromatography mass spectrometry and liquid chromatography-electrospray ionization tandem mass spectrometry.
    Anal Biochem. 2002 Jan 15;300(2):252-9 PMID: 11779118
  94. Recent advances in the biochemistry and clinical relevance of the isoprostane pathway.
    Lipids. 2005 Oct;40(10):987-94 PMID: 16382569
  95. 8-epi PGF2 alpha generation during coronary reperfusion. A potential quantitative marker of oxidant stress in vivo.
    Circulation. 1997 Jun 3;95(11):2492-9 PMID: 9184579
  96. Role of B-type natriuretic peptide (BNP) and NT-proBNP in clinical routine.
    Heart. 2006 Jun;92(6):843-9 PMID: 16698841
  97. Validation of a novel ELISA for measurement of MDA-LDL in human plasma.
    Free Radic Biol Med. 2003 Sep 1;35(5):517-27 PMID: 12927601
  98. Identification of alpha-chloro fatty aldehydes and unsaturated lysophosphatidylcholine molecular species in human atherosclerotic lesions.
    Circulation. 2003 Dec 23;108(25):3128-33 PMID: 14638540
  99. TBARS and cardiovascular disease in a population-based sample.
    J Cardiovasc Risk. 2001 Aug;8(4):219-25 PMID: 11551000
  100. Glutathione peroxidase 1 activity and cardiovascular events in patients with coronary artery disease.
    N Engl J Med. 2003 Oct 23;349(17):1605-13 PMID: 14573732
  101. A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism.
    Proc Natl Acad Sci U S A. 1990 Dec;87(23):9383-7 PMID: 2123555
Article Info
Journal
Redox biology
Abbr.
Redox Biol
ISSN
2213-2317
DOI
10.1016/j.redox.2013.07.006
Published
2013-10-08
Epub
2013-00-08
Pages
483-91
Language
English
Region
Netherlands
NLM ID
101605639
PMCID
PMC3830063
Subset
IM
External Links
PubMed source DOI: 10.1016/j.redox.2013.07.006 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2