Skip to main content
SpringerLink
Log in
Book cover

Studies on Cardiovascular Disorders pp 263–279Cite as

Oxidative Stress and Cardiovascular Disease in Diabetes Mellitus

  • Chapter
  • First Online:

Abstract

Diabetes has a profound impact on the cardiovascular system, and oxidative stress is likely an important mechanism through which diabetes adversely affects that system. Numerous animal and some human studies support the role of oxidative stress as a unifying hypothesis linking hyperglycemia to distinct cardiovascular pathophysiologic processes. The ultimate mechanism of excess production of ROS in diabetes likely involves multiple enzymatic sources of ROS that are both convergent upon common cellular and molecular targets and interrelated with positive feedback loops occurring between these different enzymatic systems. Particular roles of mitochondrial electron transport chain, Nox family NADPH oxidases, and uncoupled NO synthase(s) have been documented. While the experimental data linking oxidative stress to the cardiovascular complications of diabetes are quite extensive, as is the case in many other settings, there is a lack of convincing data in humans demonstrating a protective effect of antioxidants on diabetic cardiovascular disease. Nonetheless, strategies to reduce disrupted redox cell signaling and oxidative stress may find applicability regarding the treatment and prevention of the cardiovascular complications of diabetes.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   299.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Gan D (ed) (2006) Diabetes epidemic out of control, in diabetes atlas. International Diabetes Federation, Cape Town

    Google Scholar 

  2. Diabetes Public Health Resource (2005) National Diabetes Fact Sheet. http://www.cdc.gov/diabetes/pubs/general.htm#what. Accessed 20 Dec 2005

  3. Haidara M, Yassin HZ, Rateb M, Ammar H, Zorkani MA (2006) Role of oxidative stress in development of cardiovascular complications in diabetes mellitus. Curr Vasc Pharmacol 4(3):215–227

    Article  PubMed  CAS  Google Scholar 

  4. Boudina S, Abel ED (2007) Diabetic cardiomyopathy revisited. Circulation 115(25):3213–3223

    Article  PubMed  Google Scholar 

  5. Laakso M (1997) Epidemiology of macrovascular disease in diabetes. Diabetes Rev 5:284–315

    Google Scholar 

  6. Pandolfi A, De Filippis EA (2007) Chronic hyperglicemia and nitric oxide bioavailablity play a pivotal role in pro-atherogenic vascular modifications. Genes Nutr 2:195–208

    Article  PubMed  CAS  Google Scholar 

  7. Hink U, Li H, Mollnau H, Oelze M, Matheis E, Hartmann M, Skatchkov M, Thaiss F, Stahl RA, Warnholtz A, Meinertz T, Griendling K, Harrison DG, Forstermann U, Munzel T (2001) Mechanisms underlying endothelial dysfunction in diabetes mellitus. Circ Res 88:e14–e22

    Article  PubMed  CAS  Google Scholar 

  8. Xia P, Inoguchi T, Kern TS, Engerman RL, Oates PJ, King GL (1994) Characterization of the mechanism for the chronic activation of diacylglycerol-protein kinase C pathway in diabetes and hypergalactosemia. Diabetes 43:1122–1129

    Article  PubMed  CAS  Google Scholar 

  9. Rask-Madsen C, King GL (2005) Proatherosclerotic mechanisms involving protein kinase C in diabetes and insulin resistance. Arterioscler Thromb Vasc Biol 25(3):487–496

    Article  PubMed  CAS  Google Scholar 

  10. Hadi H, Suwaidi JA (2007) Endothelial dysfunction in diabetes mellitus. Vasc Health Risk Manag 3(6):853–876

    PubMed  CAS  Google Scholar 

  11. Ishii H, Koya D, King GL (1998) Protein kinase C activation and its role in the development of vascular complications in diabetes mellitus. J Mol Med 76:21–31

    Article  PubMed  CAS  Google Scholar 

  12. Hirata K, Hirata K, Kuroda R, Sakoda T, Katayama M, Inoue N, Suematsu M, Kawashima S, Yokoyama M (1995) Inhibition of endothelial nitric oxide synthase activity by protein kinase C. Hypertension 25:180–185

    Article  PubMed  CAS  Google Scholar 

  13. Cosentino F, Hishikawa K, Katusic ZS, Lüscher TF (1997) High glucose increases nitric oxide synthase expression and superoxide anion generation in human aortic endothelial cells. Circulation 96:25–28

    Article  PubMed  CAS  Google Scholar 

  14. Cave A, Brewer AC, Narayanapanicker A, Ray R, Grieve DJ, Walker S, Shah AM (2006) NADPH oxidases in cardiovascular health and disease. Antiox Redox Signal 8(5–6):691–728

    CAS  Google Scholar 

  15. Dinauer M, Orkin SH (1992) Chronic granulomatous disease. Annu Rev Med 43:117–124

    Article  PubMed  CAS  Google Scholar 

  16. Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414(6865):813–820

    Article  PubMed  CAS  Google Scholar 

  17. Du XL, Edelstein D, Rossetti L, Fantus IG, Goldberg H, Ziyadeh F, Wu J, Brownlee M (2000) Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc Natl Acad Sci USA 97(22):12222–12226

    Article  PubMed  CAS  Google Scholar 

  18. Subramaniam P (2007) Mechanisms for oxidative stress in diabetic cardiovascular disease. Antiox Redox Signal 9(7):955–969

    Article  Google Scholar 

  19. Salvemini D, Wang ZQ, Zweier JL, Samouilov A, Macarthur H, Misko TP, Currie MG, Cuzzocrea S, Sikorski JA, Riley DP (1999) A nonpeptidyl mimic of superoxide disutase with therapeutic activity in rats. Science 286:304–306

    Article  PubMed  CAS  Google Scholar 

  20. Stern D, Yan SD, Yan SF, Schmidt AM (2002) Receptor for advanced glycation endproducts: a multiligand receptor magnifying cell stress in diverse pathologic settings. Adv Drug Deliv Rev 54:1615–1625

    Article  PubMed  CAS  Google Scholar 

  21. Cifuentes ME, Rey FE, Carretero OA, Pagano PJ (2000) Upregulation of p67phox and gp91phox in aortas from angiotensin II-infused mice. Am J Physiol Heart Circ Physiol 279:H2234–H2240

    PubMed  CAS  Google Scholar 

  22. Meerarani P, Badimon JJ, Zias E, Fuster V, Moreno PR (2006) Metabolic syndrome and diabetic atherothrombosis: implications in vascular complications. Curr Mol Med 6:501–514

    Article  PubMed  CAS  Google Scholar 

  23. Basta G, Lazzerini G, Del Turco S, Ratto GM, Schmidt AM, De Caterina R (2005) At least 2 distinct pathways generating reactive oxygen species mediate vascular cell adhesion molecule-1 induction by advanced glycation end products. Arterioscler Thromb Vasc Biol 25:1401–1407

    Article  PubMed  CAS  Google Scholar 

  24. Lee AY, Chung SK, Chung SS (1995) Demonstration that the polyol accumulation is responsible fro diabetic cataract by the use of transgenic mice expressing the aldose reductase gene in the lens. Proc Natl Acad Sci USA 92:2780–2784

    Article  PubMed  CAS  Google Scholar 

  25. Wilson DK, Bohren KM, Gabbay KH, Quiocho FA (1992) An unlikely sugar substrate site in the 1.65 A structure of the human aldose reductase holoenzyme implicated in diabetic complications. Science 257:81–84

    Article  PubMed  CAS  Google Scholar 

  26. Morré DM, Lenaz G, Morré DJ (2000) Surface oxidase and oxidative stress propagation in aging. J Exp Biol 203:1513–1521

    PubMed  Google Scholar 

  27. Griendling KK, Sorescu D, Lassègue B, Ushio-Fukai M (2000) Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology. Arterioscler Thromb Vasc Biol 20:2175–2183

    Article  PubMed  CAS  Google Scholar 

  28. Schafer A, Bauersachs J (2008) Endothelial dysfunction, impaired endogenous platelet inhibition and platelet activation in diabetes and atherosclerosis. Curr Vasc Pharmacol 6:52–60

    Article  PubMed  Google Scholar 

  29. Munzel T, Daiber A, Ullrich V, Mülsch A (2005) Vascular consequences of endothelial nitric oxide synthase uncoupling for the activity and expression of the soluble guanylyl cyclase and the cGMP-dependent protein kinase. Arterioscler Thromb Vasc Biol 25:1551–1557

    Article  PubMed  Google Scholar 

  30. Smolenski A, Bachmann C, Reinhard K, Hönig-Liedl P, Jarchau T, Hoschuetzky H, Walter U (1998) Analysis and regulation of vasodilator-stimulated phosphoprotein serine 239 phosphorylation in vitro and in intact cells using a phosphospecific monoclonal antibody. J Bio Chem 273:20029–20035

    Article  CAS  Google Scholar 

  31. Wassman S, Nickenig G (2006) Pathophysiological regulation for the AT1-receptor and implications for vascular disease. J Hypertens Suppl 24:s15–s21

    Article  Google Scholar 

  32. Banday AA, Lokhandwala MF (2008) Oxidative stress-induced renal angiotensin AT1 receptor upregulation causes increased stimulation of sodium transporters and hypertension. Am J Physiol Renal Physiol 295:F698–F706

    Article  PubMed  CAS  Google Scholar 

  33. Nickenig G, Harrison DG (2002) The AT(1)-type angiotensin receptor in oxidative stress and atherogenesis: part I: oxidative stress and atherogenesis. Circulation 105:393–396

    Article  PubMed  CAS  Google Scholar 

  34. Wolfe ML, Iqbal N, Gefter W, Mohler ER 3rd, Rader DJ, Reilly MP (2002) Coronary artery calcification at electron beam computed tomography is increased in asymptomatic type 2 diabetics independent of traditional risk factors. J Cardiovasc Risk 9:369–376

    Article  PubMed  Google Scholar 

  35. Mosse PR, Campbell GR, Wang ZL, Campbell JH (1985) Smooth muscle phenotypic expression in human carotid arteries. I. Comparison of cells with diffuse intial thickenings adjacent to atheromatous plaques with those of the media. Lab Invest 53:556–562

    PubMed  CAS  Google Scholar 

  36. Schwartz CJ, Valente AJ, Sprague EA, Kelley JL, Cayatte AJ, Rozek MM (1992) Pathogenesis of the atherosclerotic lesion. Implications for diabetes mellitus. Diabetes Care 15:1156–1167

    Article  PubMed  CAS  Google Scholar 

  37. Suzuki LA, Poot M, Gerrity RG, Bornfeldt KE (2001) Diabetes accelerates smooth muscle accumulation in lesions of atherosclerosis: lack of direct growth-promoting effects of high glucose levels. Diabetes 50(4):851–860

    Article  PubMed  CAS  Google Scholar 

  38. Witztum JL, Steinberg D (1991) Role of oxidized low density lipoprotein in atherogenesis. J Clin Invest 88:1785–1792

    Article  PubMed  CAS  Google Scholar 

  39. Pennathur S, Ido Y, Heller JI, Byun J, Danda R, Pergola P, Williamson JR, Heinecke JW (2005) Reactive carbonyls and polyunsaturated fatty acids produce a hydroxyl radical-like species: a potential pathway for oxidative damage of retinal proteins in diabetes. J Bio Chem 280:22706–22714

    Article  CAS  Google Scholar 

  40. Steinbrecher U, Parthasarathy S, Leake DS, Witztum JL, Steinberg D (1984) Modification of low density lipoprotein by endothelial cells involves lipid peroxidation and degradation of low density lipoprotein phospholipids. Proc Natl Acad Sci USA 81:3883–3887

    Article  PubMed  CAS  Google Scholar 

  41. Steinberg D (1997) Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem 272:20963–20966

    Article  PubMed  CAS  Google Scholar 

  42. Mehta JL, Rasouli N, Sinha AK, Molavi B (2006) Oxidative stress in diabetes: a mechanistic overview of its effects on atherogenesis and myocardial dysfunction. Int J Biochem Cell Biol 38(5–6):794–803

    Article  PubMed  CAS  Google Scholar 

  43. Herkert O, Djordjevic T, BelAiba RS, Görlach A (2004) Insights into the redox control of blood coagulation: role of vascular NADPH oxidase-derived reactive oxygen species in the thrombogenic cycle. Antiox Redox Signal 6(4):765–776

    Article  CAS  Google Scholar 

  44. Kannel WB, McGee DL (1979) Diabetes and cardiovascular disease: the Framingham study. J Am Med Assoc 241:2035–2038

    Article  CAS  Google Scholar 

  45. Liu JE, Palmieri V, Roman MJ, Bella JN, Fabsitz R, Howard BV, Welty TK, Lee ET, Devereux RB (2001) The impact of diabetes on left ventricular filling pattern in normotensive and hypertensive adults: the Strong Heart Study. J Am Coll Cardiol 37:1943–1949

    Article  PubMed  CAS  Google Scholar 

  46. Schannwell CM, Schneppenheim M, Perings S, Plehn G, Strauer BE (2002) Left ventricular diastolic dysfuntion as an early manifestation of diabetic cardiomyopathy. Cardiology 98:33–39

    Article  PubMed  CAS  Google Scholar 

  47. Srikanthan P, Hsueh W (2004) Preventing heart failure in patients with diabetes. Med Clin North Am 88:1237–1256

    Article  PubMed  CAS  Google Scholar 

  48. Wold LE, Ceylan-Isik AF, Ren J (2005) Oxidative stress and stress signaling: menace of diabetic cardiomyopathy. Acta Pharmacol Sin 26(8):908–917

    Article  PubMed  CAS  Google Scholar 

  49. Adeghate E (2004) Molecular and cellular basis of the aetiology and management of diabetic cardiomyopathy: a short review. Mol Cell Biochem 261:187–191

    Article  PubMed  CAS  Google Scholar 

  50. Barouch L, Berkowitz DE, Harrison RW, O’Donnell CP, Hare JM (2003) Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice. Circulation 108:754–759

    Article  PubMed  CAS  Google Scholar 

  51. Shen X, Zheng S, Metreveli NS, Epstein PN (2006) Protection of cardiac mitochondria by overexpression of MnSOD reduces diabetic cardiomyopathy. Diabetes 55:798–805

    Article  PubMed  CAS  Google Scholar 

  52. Kjekshus J (1990) Arrhythmias and mortality in congestive heart failure. Am J Cardiol 65:I-42–I-48

    Article  Google Scholar 

  53. Tomaselli G, Marbán E (1999) Electrophysiological remodeling in hypertrophy and heart failure. Cardiovasc Res 42:270–283

    Article  PubMed  CAS  Google Scholar 

  54. Rozanski GJ, Xu Z (2002) A metabolic mechanism for cardiac K+ channel remodelling. Clin Exp Pharmacol Physiol 29:132–137

    Article  PubMed  CAS  Google Scholar 

  55. Meister A (1995) Glutathione metabolism. Meth Enzymol 251:3–7

    Article  PubMed  CAS  Google Scholar 

  56. Xu Z (1999) Interaction of glucose and glutathione metabolism in regulating K+ channels in diabetic cardiomyocytes. FASEB J 13:A97

    Google Scholar 

  57. Xu Z, Patel KP, Rozanski GJ (1996) Metabolic basis of decreased transient outward K+ current in ventricular myocytes from diabetic rats. Am J Physiol 271:H2190–H2196

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Medicine, The Atlanta VA Medical Center, Emory University School of Medicine, Atlanta, GA, USA

    Divya Gupta & Kathy K. Griendling

  2. Departments of Medicine and Biomedical Engineering, The Atlanta VA Medical Center, Emory University School of Medicine, Atlanta, GA, USA

    W. Robert Taylor

Authors
  1. Divya Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kathy K. Griendling
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W. Robert Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Divya Gupta .

Editor information

Editors and Affiliations

  1. Physiologisches Institut, Universität Gießen, Aulweg 129, Gießen, 35392, Germany

    Heinrich Sauer

  2. James Black Centre, King's College, London, Coldharbour Lane 125, London, SE5 9NU, United Kingdom

    Ajay M. Shah

  3. Fac. Medicina, Instituto do Coração (INCOR), Universidade de São Paulo, Av. Enéas de Carvalho Aguiar 44, São Paulo, 05403-000, São Paulo, Brazil

    Francisco R. M. Laurindo

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Gupta, D., Griendling, K.K., Taylor, W.R. (2010). Oxidative Stress and Cardiovascular Disease in Diabetes Mellitus. In: Sauer, H., Shah, A., Laurindo, F. (eds) Studies on Cardiovascular Disorders. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-600-9_14

Download citation

Publish with us

Policies and ethics

Search

Navigation