Skip to main content
SpringerLink
Log in

The Role of Inflammation in Type 2 Diabetes-Driven Atherosclerosis

  • Chapter
  • First Online:
Diabetic Cardiomyopathy

Part of the book series: Advances in Biochemistry in Health and Disease ((ABHD,volume 9))

  • 7326 Accesses

Abstract

Cardiovascular disease is the most frequent and costly complication of type 2 diabetes (T2D). Inflammation is a shared feature of T2D and cardiovascular disease. Vascular and obesity-mediated inflammation may be key processes responsible for the accelerated development of atherosclerosis in individuals with T2D. Atherosclerosis begins with an insult to the endothelium and progresses through several stages, including the development of endothelial dysfunction, the accumulation of lipids and immune cells in the vessel intima, and phenotypic changes to the vascular cells, all contributing to the formation of vascular lesions. Inflammation plays a central role in many of these phases. The metabolic imbalances characteristic of T2D, such as insulin resistance, hyperglycemia, and hyperlipidemia, exacerbate vascular dysfunction and inflammation, accelerating the progression to advanced atherosclerosis. The expression and production of circulating cytokines and adipokines are altered in T2D, contributing to the proinflammatory state in blood vessels and adipose tissue. Epigenetic mechanisms are emerging as a missing link in diabetes etiology and may contribute to accelerated atherosclerosis. Two other forms of vascular disease, restenosis and graft vascular disease, share features with atherosclerosis. The presence of T2D similarly worsens these conditions, putting these individuals at risk for major adverse cardiac events. Further study of the inflammatory mechanisms and epigenetics will improve our understanding of the role of inflammation in T2D and accelerated cardiovascular disease, and may provide new personalized therapies to treat these conditions.

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

Access this chapter

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 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

Institutional subscriptions

References

  1. Bandyopadhyay P (2006) Cardiovascular diseases and diabetes mellitus. Drug News Perspect 19:369–375

    PubMed  Google Scholar 

  2. Wild S, Roglic G, Green A et al (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:1047–1053

    PubMed  Google Scholar 

  3. Tavani A, Bertuzzi M, Gallus S et al (2002) Diabetes mellitus as a contributor to the risk of acute myocardial infarction. J Clin Epidemiol 55:1082–1087

    PubMed  Google Scholar 

  4. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) (2002) Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation 106:3143–3421

    Google Scholar 

  5. De Backer G, Ambrosioni E, Borch-Johnsen K et al (2003) European guidelines on cardiovascular disease prevention in clinical practice: third joint task force of European and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of eight societies and by invited experts). Eur J Cardiovasc Prev Rehabil 10:S1–S10

    PubMed  Google Scholar 

  6. Festa A, D’Agostino R Jr, Howard G et al (2000) Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation 102:42–47

    CAS  PubMed  Google Scholar 

  7. Hak AE, Stehouwer CD, Bots ML et al (1999) Associations of C-reactive protein with measures of obesity, insulin resistance, and subclinical atherosclerosis in healthy, middle-aged women. Arterioscler Thromb Vasc Biol 19:1986–1991

    CAS  PubMed  Google Scholar 

  8. Perrault R, Zahradka P (2011) Vascular dysfunction in heart disease. In: Dhalla NS, Nagano M, Ostadal B (eds) Molecular defects in cardiovascular disease. Springer, New York, pp 283–303

    Google Scholar 

  9. Romeo GR, Lee J, Shoelson SE (2012) Metabolic syndrome, insulin resistance, and roles of inflammation—mechanisms and therapeutic targets. Arterioscler Thromb Vasc Biol 32:1771–1776

    CAS  PubMed  Google Scholar 

  10. Wellen KE, Hotamisligil GS (2005) Inflammation, stress, and diabetes. J Clin Invest 115:1111–1119

    CAS  PubMed Central  PubMed  Google Scholar 

  11. Puri R, Kataoka Y, Uno K et al (2012) The distinctive nature of atherosclerotic vascular disease in diabetes: pathophysiological and morphological insights. Curr Diab Rep 12:280–285

    CAS  PubMed  Google Scholar 

  12. Tousoulis D, Kampoli AM, Papageorgiou N et al (2011) Pathophysiology of atherosclerosis: the role of inflammation. Curr Pharm Des 17:4089–4110

    CAS  PubMed  Google Scholar 

  13. Goldschmidt-Clermont PJ, Dong C, Seo DM et al (2012) Atherosclerosis, inflammation, genetics, and stem cells: 2012 update. Curr Atheroscler Rep 14:201–210

    CAS  PubMed Central  PubMed  Google Scholar 

  14. Hotamisligil GS, Erbay E (2008) Nutrient sensing and inflammation in metabolic diseases. Nat Rev Immunol 8:923–934

    CAS  PubMed Central  PubMed  Google Scholar 

  15. Donath MY, Shoelson SE (2011) Type 2 diabetes as an inflammatory disease. Nat Rev Immunol 11:98–107

    CAS  PubMed  Google Scholar 

  16. Ross R (1999) Atherosclerosis—an inflammatory disease. N Engl J Med 340:115–126

    CAS  PubMed  Google Scholar 

  17. Hahn C, Schwartz MA (2009) Mechanotransduction in vascular physiology and atherogenesis. Nat Rev Mol Cell Biol 10:53–62

    CAS  PubMed Central  PubMed  Google Scholar 

  18. Santos MG, Pegoraro M, Sandrini F et al (2008) Risk factors for the development of atherosclerosis in childhood and adolescence. Arq Bras Cardiol 90:276–283

    PubMed  Google Scholar 

  19. American Heart Association (2013) Risk factors and coronary heart disease. http://www.americanheart.org/presenter.jhtml?identifier=4726. Accessed 24 Jan 2013

  20. Katsiki N, Tziomalos K, Chatzizisis Y et al (2010) Effect of HMG-CoA reductase inhibitors on vascular cell apoptosis: beneficial or detrimental? Atherosclerosis 211:9–14

    CAS  PubMed  Google Scholar 

  21. Woollard KJ, Geissmann F (2010) Monocytes in atherosclerosis: subsets and functions. Nat Rev Cardiol 7:77–86

    PubMed Central  PubMed  Google Scholar 

  22. Yu J, Li Y, Li M et al (2010) Oxidized low density lipoprotein-induced transdifferentiation of bone marrow-derived smooth muscle-like cells into foam-like cells in vitro. Int J Exp Pathol 91:24–33

    CAS  PubMed Central  PubMed  Google Scholar 

  23. Ross R, Glomset JA (1973) Atherosclerosis and the arterial smooth muscle cell: proliferation of smooth muscle is a key event in the genesis of the lesions of atherosclerosis. Science 180:1332–1339

    CAS  PubMed  Google Scholar 

  24. Shah PK (2003) Pathophysiology of plaque rupture and the concept of plaque stabilization. Cardiol Clin 21:303–314, v

    PubMed  Google Scholar 

  25. Davies MJ, Thomas A (1984) Thrombosis and acute coronary-artery lesions in sudden cardiac ischemic death. N Engl J Med 310:1137–1140

    CAS  PubMed  Google Scholar 

  26. Tabit CE, Chung WB, Hamburg NM et al (2010) Endothelial dysfunction in diabetes mellitus: molecular mechanisms and clinical implications. Rev Endocr Metab Disord 11:61–74

    CAS  PubMed Central  PubMed  Google Scholar 

  27. Ku DN, Giddens DP, Zarins CK et al (1985) Pulsatile flow and atherosclerosis in the human carotid bifurcation. Positive correlation between plaque location and low oscillating shear stress. Arteriosclerosis 5:293–302

    CAS  PubMed  Google Scholar 

  28. Chien S (2008) Role of shear stress direction in endothelial mechanotransduction. Mol Cell Biomech 5:1–8

    PubMed  Google Scholar 

  29. Wolin MS (2009) Reactive oxygen species and the control of vascular function. Am J Physiol Heart Circ Physiol 296:H539–H549

    CAS  PubMed  Google Scholar 

  30. Ley K, Miller YI, Hedrick CC (2011) Monocyte and macrophage dynamics during atherogenesis. Arterioscler Thromb Vasc Biol 31:1506–1516

    CAS  PubMed Central  PubMed  Google Scholar 

  31. Kuckleburg CJ, Yates CM, Kalia N et al (2011) Endothelial cell-borne platelet bridges selectively recruit monocytes in human and mouse models of vascular inflammation. Cardiovasc Res 91:134–141

    CAS  PubMed  Google Scholar 

  32. Furman MI, Benoit SE, Barnard MR et al (1998) Increased platelet reactivity and circulating monocyte-platelet aggregates in patients with stable coronary artery disease. J Am Coll Cardiol 31:352–358

    CAS  PubMed  Google Scholar 

  33. Doran AC, Meller N, McNamara CA (2008) Role of smooth muscle cells in the initiation and early progression of atherosclerosis. Arterioscler Thromb Vasc Biol 28:812–819

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Garin G, Berk BC (2006) Flow-mediated signaling modulates endothelial cell phenotype. Endothelium 13:375–384

    CAS  PubMed  Google Scholar 

  35. Chiu JJ, Chien S (2011) Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiol Rev 91:327–387

    PubMed  Google Scholar 

  36. Pierce AD, Anglin IE, Vitolo MI et al (2012) Glucose-activated RUNX2 phosphorylation promotes endothelial cell proliferation and an angiogenic phenotype. J Cell Biochem 113:282–292

    CAS  PubMed Central  PubMed  Google Scholar 

  37. Simmons GH, Padilla J, Laughlin MH (2012) Heterogeneity of endothelial cell phenotype within and amongst conduit vessels of the swine vasculature. Exp Physiol 97:1074–1082

    CAS  PubMed  Google Scholar 

  38. Versari D, Daghini E, Virdis A et al (2009) Endothelial dysfunction as a target for prevention of cardiovascular disease. Diabetes Care 32(Suppl 2):S314–S321

    CAS  PubMed  Google Scholar 

  39. Vasquez-Vivar J, Kalyanaraman B, Martasek P et al (1998) Superoxide generation by endothelial nitric oxide synthase: the influence of cofactors. Proc Natl Acad Sci U S A 95:9220–9225

    CAS  PubMed Central  PubMed  Google Scholar 

  40. White MF (1997) The insulin signalling system and the IRS proteins. Diabetologia 40(Suppl 2):S2–S17

    CAS  PubMed  Google Scholar 

  41. Muniyappa R, Montagnani M, Koh KK et al (2007) Cardiovascular actions of insulin. Endocr Rev 28:463–491

    CAS  PubMed  Google Scholar 

  42. Kuboki K, Jiang ZY, Takahara N et al (2000) Regulation of endothelial constitutive nitric oxide synthase gene expression in endothelial cells and in vivo: a specific vascular action of insulin. Circulation 101:676–681

    CAS  PubMed  Google Scholar 

  43. Moncada S, Higgs EA (2006) Nitric oxide and the vascular endothelium. Handb Exp Pharmacol 176:213–254

    PubMed  Google Scholar 

  44. Hsueh WA, Quinones MJ (2003) Role of endothelial dysfunction in insulin resistance. Am J Cardiol 92:10J–17J

    CAS  PubMed  Google Scholar 

  45. Christlieb AR, Janka HU, Kraus B et al (1976) Vascular reactivity to angiotensin II and to norepinephrine in diabetic subjects. Diabetes 25:268–274

    CAS  PubMed  Google Scholar 

  46. Tesfamariam B, Brown ML, Deykin D et al (1990) Elevated glucose promotes generation of endothelium-derived vasoconstrictor prostanoids in rabbit aorta. J Clin Invest 85:929–932

    CAS  PubMed Central  PubMed  Google Scholar 

  47. Wheatcroft SB, Williams IL, Shah AM et al (2003) Pathophysiological implications of insulin resistance on vascular endothelial function. Diabet Med 20:255–268

    CAS  PubMed  Google Scholar 

  48. Diez J (2007) Arterial stiffness and extracellular matrix. Adv Cardiol 44:76–95

    CAS  PubMed  Google Scholar 

  49. Fleenor BS, Sindler AL, Eng JS et al (2012) Sodium nitrite de-stiffening of large elastic arteries with aging: role of normalization of advanced glycation end-products. Exp Gerontol 47:588–594

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Farmer DG, Kennedy S (2009) RAGE, vascular tone and vascular disease. Pharmacol Ther 124:185–194

    CAS  PubMed  Google Scholar 

  51. Burke AP, Kolodgie FD, Zieske A et al (2004) Morphologic findings of coronary atherosclerotic plaques in diabetics: a postmortem study. Arterioscler Thromb Vasc Biol 24:1266–1271

    CAS  PubMed  Google Scholar 

  52. Nishikawa T, Edelstein D, Brownlee M (2000) The missing link: a single unifying mechanism for diabetic complications. Kidney Int Suppl 77:S26–S30

    CAS  PubMed  Google Scholar 

  53. Talayero BG, Sacks FM (2011) The role of triglycerides in atherosclerosis. Curr Cardiol Rep 13:544–552

    PubMed Central  PubMed  Google Scholar 

  54. Li H, Li H, Bao Y et al (2011) Free fatty acids induce endothelial dysfunction and activate protein kinase C and nuclear factor-kappaB pathway in rat aorta. Int J Cardiol 152:218–224

    PubMed  Google Scholar 

  55. Dimmeler S, Hermann C, Zeiher AM (1998) Apoptosis of endothelial cells. Contribution to the pathophysiology of atherosclerosis? Eur Cytokine Netw 9:697–698

    CAS  PubMed  Google Scholar 

  56. Foteinos G, Hu Y, Xiao Q et al (2008) Rapid endothelial turnover in atherosclerosis-prone areas coincides with stem cell repair in apolipoprotein E-deficient mice. Circulation 117:1856–1863

    PubMed  Google Scholar 

  57. van der Giessen AG, Wentzel JJ, Meijboom WB et al (2009) Plaque and shear stress distribution in human coronary bifurcations: a multislice computed tomography study. EuroIntervention 4:654–661

    PubMed  Google Scholar 

  58. Hilgers RH, Webb RC (2005) Molecular aspects of arterial smooth muscle contraction: focus on Rho. Exp Biol Med (Maywood) 230:829–835

    CAS  Google Scholar 

  59. Mallika V, Goswami B, Rajappa M (2007) Atherosclerosis pathophysiology and the role of novel risk factors: a clinicobiochemical perspective. Angiology 58:513–522

    CAS  PubMed  Google Scholar 

  60. Muto A, Fitzgerald TN, Pimiento JM et al (2007) Smooth muscle cell signal transduction: implications of vascular biology for vascular surgeons. J Vasc Surg 45(Suppl A):A15–A24

    PubMed  Google Scholar 

  61. Rudd JHF, Weissberg PL (2002) Atherosclerosis. In: Hunt BJ, Poston L, Schachter M et al (eds) An introduction to vascular biology, 2nd edn. Cambridge University Press, Cambridge, p 302

    Google Scholar 

  62. Owens GK (1996) Chapter 23: Role of alterations in the differentiated state of vascular smooth muscle cells in atherogenesis. In: Fuster V, Ross R, Topol EJ (eds) Atherosclerosis and coronary artery disease. Lippincott-Raven, Philadelphia, p 401

    Google Scholar 

  63. Bennett MR (1999) Apoptosis of vascular smooth muscle cells in vascular remodelling and atherosclerotic plaque rupture. Cardiovasc Res 41:361–368

    CAS  PubMed  Google Scholar 

  64. Choudhury RP, Lee JM, Greaves DR (2005) Mechanisms of disease: macrophage-derived foam cells emerging as therapeutic targets in atherosclerosis. Nat Clin Pract Cardiovasc Med 2:309–315

    CAS  PubMed  Google Scholar 

  65. Davies MJ, Richardson PD, Woolf N et al (1993) Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. Br Heart J 69:377–381

    CAS  PubMed Central  PubMed  Google Scholar 

  66. Mosser DM, Edwards JP (2008) Exploring the full spectrum of macrophage activation. Nat Rev Immunol 8:958–969

    CAS  PubMed Central  PubMed  Google Scholar 

  67. Schmidt AM, Stern D (2000) Atherosclerosis and diabetes: the RAGE connection. Curr Atheroscler Rep 2:430–436

    CAS  PubMed  Google Scholar 

  68. Weisberg SP, McCann D, Desai M et al (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112:1796–1808

    CAS  PubMed Central  PubMed  Google Scholar 

  69. Voll RE, Urbonaviciute V (2008) High mobility group box 1 in the pathogenesis of inflammatory and autoimmune diseases. Isr Med Assoc J 10:26–28

    PubMed  Google Scholar 

  70. Xu H, Barnes GT, Yang Q et al (2003) Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112:1821–1830

    CAS  PubMed Central  PubMed  Google Scholar 

  71. DeClercq V, Taylor C, Zahradka P (2008) Adipose tissue: the link between obesity and cardiovascular disease. Cardiovasc Hematol Disord Drug Targets 8:228–237

    CAS  PubMed  Google Scholar 

  72. Declercq V, Enns J, Yeganeh A et al (2013) Modulation of cardiovascular function by adipokines. Cardiovasc Hematol Disord Drug Targets 13:59–72

    CAS  PubMed  Google Scholar 

  73. Northcott JM, Yeganeh A, Taylor CG et al (2012) Adipokines and the cardiovascular system: mechanisms mediating health and disease. Can J Physiol Pharmacol 90:1029–1059

    CAS  PubMed  Google Scholar 

  74. Sengenes C, Miranville A, Lolmede K et al (2007) The role of endothelial cells in inflamed adipose tissue. J Intern Med 262:415–421

    CAS  PubMed  Google Scholar 

  75. England RN, Autieri MV (2012) Anti-inflammatory effects of interleukin-19 in vascular disease. Int J Inflam 2012:253583

    PubMed Central  PubMed  Google Scholar 

  76. Coppack SW (2001) Pro-inflammatory cytokines and adipose tissue. Proc Nutr Soc 60:349–356

    CAS  PubMed  Google Scholar 

  77. Paukku K, Silvennoinen O (2004) STATs as critical mediators of signal transduction and transcription: lessons learned from STAT5. Cytokine Growth Factor Rev 15:435–455

    CAS  PubMed  Google Scholar 

  78. Brand K, Page S, Walli AK et al (1997) Role of nuclear factor-kappa B in atherogenesis. Exp Physiol 82:297–304

    CAS  PubMed  Google Scholar 

  79. Hansson GK, Libby P (2006) The immune response in atherosclerosis: a double-edged sword. Nat Rev Immunol 6:508–519

    CAS  PubMed  Google Scholar 

  80. Frostegard J, Ulfgren AK, Nyberg P et al (1999) Cytokine expression in advanced human atherosclerotic plaques: dominance of pro-inflammatory (Th1) and macrophage-stimulating cytokines. Atherosclerosis 145:33–43

    CAS  PubMed  Google Scholar 

  81. von der Thusen JH, Kuiper J, van Berkel TJ et al (2003) Interleukins in atherosclerosis: molecular pathways and therapeutic potential. Pharmacol Rev 55:133–166

    PubMed  Google Scholar 

  82. Juge-Aubry CE, Somm E, Chicheportiche R et al (2004) Regulatory effects of interleukin (IL)-1, interferon-beta, and IL-4 on the production of IL-1 receptor antagonist by human adipose tissue. J Clin Endocrinol Metab 89:2652–2658

    CAS  PubMed  Google Scholar 

  83. Jager J, Gremeaux T, Cormont M et al (2007) Interleukin-1beta-induced insulin resistance in adipocytes through down-regulation of insulin receptor substrate-1 expression. Endocrinology 148:241–251

    CAS  PubMed Central  PubMed  Google Scholar 

  84. Rui L, Yuan M, Frantz D et al (2002) SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2. J Biol Chem 277:42394–42398

    CAS  PubMed  Google Scholar 

  85. Eizirik DL, Mandrup-Poulsen T (2001) A choice of death: the signal-transduction of immune-mediated beta-cell apoptosis. Diabetologia 44:2115–2133

    CAS  PubMed  Google Scholar 

  86. Dinarello CA (2000) Proinflammatory cytokines. Chest 118:503–508

    CAS  PubMed  Google Scholar 

  87. Zilverschoon GR, Tack CJ, Joosten LA et al (2008) Interleukin-18 resistance in patients with obesity and type 2 diabetes mellitus. Int J Obes (Lond) 32:1407–1414

    CAS  Google Scholar 

  88. Robertson AK, Hansson GK (2006) T cells in atherogenesis: for better or for worse? Arterioscler Thromb Vasc Biol 26:2421–2432

    CAS  PubMed  Google Scholar 

  89. Leon ML, Zuckerman SH (2005) Gamma interferon: a central mediator in atherosclerosis. Inflamm Res 54:395–411

    CAS  PubMed  Google Scholar 

  90. Gerdes N, Sukhova GK, Libby P et al (2002) Expression of interleukin (IL)-18 and functional IL-18 receptor on human vascular endothelial cells, smooth muscle cells, and macrophages: implications for atherogenesis. J Exp Med 195:245–257

    CAS  PubMed Central  PubMed  Google Scholar 

  91. De Nardo D, Latz E (2011) NLRP3 inflammasomes link inflammation and metabolic disease. Trends Immunol 32:373–379

    PubMed Central  PubMed  Google Scholar 

  92. Spranger J, Kroke A, Mohlig M et al (2003) Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes 52:812–817

    CAS  PubMed  Google Scholar 

  93. Pradhan AD, Manson JE, Rifai N et al (2001) C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286:327–334

    CAS  PubMed  Google Scholar 

  94. Tzoulaki I, Murray GD, Lee AJ et al (2005) C-reactive protein, interleukin-6, and soluble adhesion molecules as predictors of progressive peripheral atherosclerosis in the general population: Edinburgh Artery Study. Circulation 112:976–983

    CAS  PubMed  Google Scholar 

  95. Senn JJ, Klover PJ, Nowak IA et al (2003) Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes. J Biol Chem 278:13740–13746

    CAS  PubMed  Google Scholar 

  96. Mooney RA, Senn J, Cameron S et al (2001) Suppressors of cytokine signaling-1 and -6 associate with and inhibit the insulin receptor. A potential mechanism for cytokine-mediated insulin resistance. J Biol Chem 276:25889–25893

    CAS  PubMed  Google Scholar 

  97. Nonogaki K, Fuller GM, Fuentes NL et al (1995) Interleukin-6 stimulates hepatic triglyceride secretion in rats. Endocrinology 136:2143–2149

    CAS  PubMed  Google Scholar 

  98. Johnson DR, O’Connor JC, Satpathy A et al (2006) Cytokines in type 2 diabetes. Vitam Horm 74:405–441

    CAS  PubMed  Google Scholar 

  99. Dandona P, Aljada A, Chaudhuri A et al (2005) Metabolic syndrome: a comprehensive perspective based on interactions between obesity, diabetes, and inflammation. Circulation 111:1448–1454

    PubMed  Google Scholar 

  100. Hotamisligil GS, Peraldi P, Budavari A et al (1996) IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science 271:665–668

    CAS  PubMed  Google Scholar 

  101. Aguirre V, Uchida T, Yenush L et al (2000) The c-Jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307). J Biol Chem 275:9047–9054

    CAS  PubMed  Google Scholar 

  102. Fard A, Tuck CH, Donis JA et al (2000) Acute elevations of plasma asymmetric dimethylarginine and impaired endothelial function in response to a high-fat meal in patients with type 2 diabetes. Arterioscler Thromb Vasc Biol 20:2039–2044

    CAS  PubMed  Google Scholar 

  103. Szekanecz Z (2008) Pro-inflammatory cytokines in atherosclerosis. Isr Med Assoc J 10:529–530

    PubMed  Google Scholar 

  104. Popa C, Netea MG, van Riel PL et al (2007) The role of TNF-alpha in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk. J Lipid Res 48:751–762

    CAS  PubMed  Google Scholar 

  105. Zernecke A, Weber C (2005) Inflammatory mediators in atherosclerotic vascular disease. Basic Res Cardiol 100:93–101

    CAS  PubMed  Google Scholar 

  106. Panee J (2012) Monocyte chemoattractant protein 1 (MCP-1) in obesity and diabetes. Cytokine 60:1–12

    CAS  PubMed Central  PubMed  Google Scholar 

  107. Haubner F, Lehle K, Munzel D et al (2007) Hyperglycemia increases the levels of vascular cellular adhesion molecule-1 and monocyte-chemoattractant-protein-1 in the diabetic endothelial cell. Biochem Biophys Res Commun 360:560–565

    CAS  PubMed  Google Scholar 

  108. Takahara N, Kashiwagi A, Nishio Y et al (1997) Oxidized lipoproteins found in patients with NIDDM stimulate radical-induced monocyte chemoattractant protein-1 mRNA expression in cultured human endothelial cells. Diabetologia 40:662–670

    CAS  PubMed  Google Scholar 

  109. Blake GJ, Ridker PM (2002) Inflammatory bio-markers and cardiovascular risk prediction. J Intern Med 252:283–294

    CAS  PubMed  Google Scholar 

  110. Chen H (2006) Cellular inflammatory responses: novel insights for obesity and insulin resistance. Pharmacol Res 53:469–477

    CAS  PubMed  Google Scholar 

  111. Paffen E, DeMaat MP (2006) C-reactive protein in atherosclerosis: a causal factor? Cardiovasc Res 71:30–39

    CAS  PubMed  Google Scholar 

  112. Krieglstein CF, Granger DN (2001) Adhesion molecules and their role in vascular disease. Am J Hypertens 14:44S–54S

    CAS  PubMed  Google Scholar 

  113. Chia MC (1998) The role of adhesion molecules in atherosclerosis. Crit Rev Clin Lab Sci 35:573–602

    CAS  PubMed  Google Scholar 

  114. Rubio-Guerra AF, Vargas-Robles H, Serrano AM et al (2009) Correlation between the levels of circulating adhesion molecules and atherosclerosis in type-2 diabetic normotensive patients: circulating adhesion molecules and atherosclerosis. Cell Adh Migr 3:369–372

    PubMed  Google Scholar 

  115. Galen FX (2002) Cell adhesion molecules in hypertension: endothelial markers of vascular injury and predictors of target organ damage? J Hypertens 20:813–816

    CAS  PubMed  Google Scholar 

  116. Rubio-Guerra AF, Vargas-Robles H, Ayala GV et al (2007) Correlation between circulating adhesion molecule levels and albuminuria in type 2 diabetic normotensive patients. Med Sci Monit 13:CR349–CR352

    CAS  PubMed  Google Scholar 

  117. Dandona P, Aljada A, Chaudhuri A et al (2003) The potential influence of inflammation and insulin resistance on the pathogenesis and treatment of atherosclerosis-related complications in type 2 diabetes. J Clin Endocrinol Metab 88:2422–2429

    CAS  PubMed  Google Scholar 

  118. Scherer PE, Williams S, Fogliano M et al (1995) A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 270:26746–26749

    CAS  PubMed  Google Scholar 

  119. Hotta K, Funahashi T, Arita Y et al (2000) Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 20:1595–1599

    CAS  PubMed  Google Scholar 

  120. Ukkola O, Santaniemi M (2002) Adiponectin: a link between excess adiposity and associated comorbidities? J Mol Med 80:696–702

    CAS  PubMed  Google Scholar 

  121. Berg AH, Combs TP, Du X et al (2001) The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 7:947–953

    CAS  PubMed  Google Scholar 

  122. Ouchi N, Kihara S, Arita Y et al (1999) Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 100:2473–2476

    CAS  PubMed  Google Scholar 

  123. Ouchi N, Kihara S, Arita Y et al (2000) Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation 102:1296–1301

    CAS  PubMed  Google Scholar 

  124. Bastard JP, Maachi M, Lagathu C et al (2006) Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw 17:4–12

    CAS  PubMed  Google Scholar 

  125. Yamawaki H (2011) Vascular effects of novel adipocytokines: focus on vascular contractility and inflammatory responses. Biol Pharm Bull 34:307–310

    CAS  PubMed  Google Scholar 

  126. Xi W, Satoh H, Kase H et al (2005) Stimulated HSP90 binding to eNOS and activation of the PI3-Akt pathway contribute to globular adiponectin-induced NO production: vasorelaxation in response to globular adiponectin. Biochem Biophys Res Commun 332:200–205

    CAS  PubMed  Google Scholar 

  127. Cheng KK, Lam KS, Wang Y et al (2007) Adiponectin-induced endothelial nitric oxide synthase activation and nitric oxide production are mediated by APPL1 in endothelial cells. Diabetes 56:1387–1394

    PubMed  Google Scholar 

  128. Yamawaki H, Tsubaki N, Mukohda M et al (2010) Omentin, a novel adipokine, induces vasodilation in rat isolated blood vessels. Biochem Biophys Res Commun 393:668–672

    CAS  PubMed  Google Scholar 

  129. Hida K, Wada J, Eguchi J et al (2005) Visceral adipose tissue-derived serine protease inhibitor: a unique insulin-sensitizing adipocytokine in obesity. Proc Natl Acad Sci U S A 102:10610–10615

    CAS  PubMed Central  PubMed  Google Scholar 

  130. Gentile MT, Vecchione C, Marino G et al (2008) Resistin impairs insulin-evoked vasodilation. Diabetes 57:577–583

    CAS  PubMed  Google Scholar 

  131. Kim SR, Bae YH, Bae SK et al (2008) Visfatin enhances ICAM-1 and VCAM-1 expression through ROS-dependent NF-kappaB activation in endothelial cells. Biochim Biophys Acta 1783:886–895

    CAS  PubMed  Google Scholar 

  132. Adya R, Tan BK, Punn A et al (2008) Visfatin induces human endothelial VEGF and MMP-2/9 production via MAPK and PI3K/Akt signalling pathways: novel insights into visfatin-induced angiogenesis. Cardiovasc Res 78:356–365

    CAS  PubMed  Google Scholar 

  133. Wang Z, Nakayama T (2010) Inflammation, a link between obesity and cardiovascular disease. Mediators Inflamm 2010:535918

    PubMed Central  PubMed  Google Scholar 

  134. Coppari R, Bjorbaek C (2012) Leptin revisited: its mechanism of action and potential for treating diabetes. Nat Rev Drug Discov 11:692–708

    CAS  PubMed  Google Scholar 

  135. Soderberg S, Ahren B, Jansson JH et al (1999) Leptin is associated with increased risk of myocardial infarction. J Intern Med 246:409–418

    CAS  PubMed  Google Scholar 

  136. Wallace AM, McMahon AD, Packard CJ et al (2001) Plasma leptin and the risk of cardiovascular disease in the West of Scotland Coronary Prevention Study (WOSCOPS). Circulation 104:3052–3056

    CAS  PubMed  Google Scholar 

  137. Singhal A, Farooqi IS, Cole TJ et al (2002) Influence of leptin on arterial distensibility: a novel link between obesity and cardiovascular disease? Circulation 106:1919–1924

    CAS  PubMed  Google Scholar 

  138. Ciccone M, Vettor R, Pannacciulli N et al (2001) Plasma leptin is independently associated with the intima-media thickness of the common carotid artery. Int J Obes Relat Metab Disord 25:805–810

    CAS  PubMed  Google Scholar 

  139. Zarkesh-Esfahani H, Pockley G, Metcalfe RA et al (2001) High-dose leptin activates human leukocytes via receptor expression on monocytes. J Immunol 167:4593–4599

    CAS  PubMed  Google Scholar 

  140. Mancuso P, Canetti C, Gottschalk A et al (2004) Leptin augments alveolar macrophage leukotriene synthesis by increasing phospholipase activity and enhancing group IVC iPLA2 (cPLA2gamma) protein expression. Am J Physiol Lung Cell Mol Physiol 287:L497–L502

    CAS  PubMed  Google Scholar 

  141. Lord GM, Matarese G, Howard JK et al (1998) Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 394:897–901

    CAS  PubMed  Google Scholar 

  142. Ling C, Groop L (2009) Epigenetics: a molecular link between environmental factors and type 2 diabetes. Diabetes 58:2718–2725

    CAS  PubMed  Google Scholar 

  143. Litherland SA (2008) Immunopathogenic interaction of environmental triggers and genetic susceptibility in diabetes: is epigenetics the missing link? Diabetes 57:3184–3186

    CAS  PubMed  Google Scholar 

  144. Luger K, Mader AW, Richmond RK et al (1997) Crystal structure of the nucleosome core particle at 2.8 Å resolution. Nature 389:251–260

    CAS  PubMed  Google Scholar 

  145. Villeneuve LM, Natarajan R (2010) The role of epigenetics in the pathology of diabetic complications. Am J Physiol Renal Physiol 299:F14–F25

    CAS  PubMed  Google Scholar 

  146. Gray SG, De Meyts P (2005) Role of histone and transcription factor acetylation in diabetes pathogenesis. Diabetes Metab Res Rev 21:416–433

    CAS  PubMed  Google Scholar 

  147. Liang F, Kume S, Koya D (2009) SIRT1 and insulin resistance. Nat Rev Endocrinol 5:367–373

    CAS  PubMed  Google Scholar 

  148. Ito K, Hanazawa T, Tomita K et al (2004) Oxidative stress reduces histone deacetylase 2 activity and enhances IL-8 gene expression: role of tyrosine nitration. Biochem Biophys Res Commun 315:240–245

    CAS  PubMed  Google Scholar 

  149. Vanden Berghe W, De Bosscher K, Boone E et al (1999) The nuclear factor-kappaB engages CBP/p300 and histone acetyltransferase activity for transcriptional activation of the interleukin-6 gene promoter. J Biol Chem 274:32091–32098

    CAS  PubMed  Google Scholar 

  150. Reddy MA, Sahar S, Villeneuve LM et al (2009) Role of Src tyrosine kinase in the atherogenic effects of the 12/15-lipoxygenase pathway in vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 29:387–393

    CAS  PubMed Central  PubMed  Google Scholar 

  151. Miao F, Gonzalo IG, Lanting L et al (2004) In vivo chromatin remodeling events leading to inflammatory gene transcription under diabetic conditions. J Biol Chem 279:18091–18097

    CAS  PubMed  Google Scholar 

  152. Chen S, Feng B, George B et al (2010) Transcriptional coactivator p300 regulates glucose-induced gene expression in endothelial cells. Am J Physiol Endocrinol Metab 298:E127–E137

    CAS  PubMed  Google Scholar 

  153. Miao F, Wu X, Zhang L et al (2007) Genome-wide analysis of histone lysine methylation variations caused by diabetic conditions in human monocytes. J Biol Chem 282:13854–13863

    CAS  PubMed  Google Scholar 

  154. Li Y, Reddy MA, Miao F et al (2008) Role of the histone H3 lysine 4 methyltransferase, SET7/9, in the regulation of NF-kappaB-dependent inflammatory genes. Relevance to diabetes and inflammation. J Biol Chem 283:26771–26781

    CAS  PubMed  Google Scholar 

  155. El-Osta A, Brasacchio D, Yao D et al (2008) Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia. J Exp Med 205:2409–2417

    CAS  PubMed Central  PubMed  Google Scholar 

  156. Brasacchio D, Okabe J, Tikellis C et al (2009) Hyperglycemia induces a dynamic cooperativity of histone methylase and demethylase enzymes associated with gene-activating epigenetic marks that coexist on the lysine tail. Diabetes 58:1229–1236

    CAS  PubMed  Google Scholar 

  157. Kuroda A, Rauch TA, Todorov I et al (2009) Insulin gene expression is regulated by DNA methylation. PLoS One 4:e6953

    PubMed Central  PubMed  Google Scholar 

  158. Morgan HD, Sutherland HG, Martin DI et al (1999) Epigenetic inheritance at the agouti locus in the mouse. Nat Genet 23:314–318

    CAS  PubMed  Google Scholar 

  159. Ingrosso D, Perna AF (2009) Epigenetics in hyperhomocysteinemic states. A special focus on uremia. Biochim Biophys Acta 1790:892–899

    CAS  PubMed  Google Scholar 

  160. Ekstrom TJ, Stenvinkel P (2009) The epigenetic conductor: a genomic orchestrator in chronic kidney disease complications? J Nephrol 22:442–449

    PubMed  Google Scholar 

  161. Jamaluddin MS, Yang X, Wang H (2007) Hyperhomocysteinemia, DNA methylation and vascular disease. Clin Chem Lab Med 45:1660–1666

    CAS  PubMed  Google Scholar 

  162. Luscher TF, Creager MA, Beckman JA et al (2003) Diabetes and vascular disease: pathophysiology, clinical consequences, and medical therapy: part II. Circulation 108:1655–1661

    PubMed  Google Scholar 

  163. Berry C, Tardif JC, Bourassa MG (2007) Coronary heart disease in patients with diabetes: part I: recent advances in prevention and noninvasive management. J Am Coll Cardiol 49:631–642

    CAS  PubMed  Google Scholar 

  164. Haffner SM, Lehto S, Ronnemaa T et al (1998) Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 339:229–234

    CAS  PubMed  Google Scholar 

  165. Jonas M, Edelman ER, Groothuis A et al (2005) Vascular neointimal formation and signaling pathway activation in response to stent injury in insulin-resistant and diabetic animals. Circ Res 97:725–733

    CAS  PubMed  Google Scholar 

  166. Morss AS, Edelman ER (2007) Glucose modulates basement membrane fibroblast growth factor-2 via alterations in endothelial cell permeability. J Biol Chem 282:14635–14644

    CAS  PubMed  Google Scholar 

  167. Piatti P, Di Mario C, Monti LD et al (2003) Association of insulin resistance, hyperleptinemia, and impaired nitric oxide release with in-stent restenosis in patients undergoing coronary stenting. Circulation 108:2074–2081

    CAS  PubMed  Google Scholar 

  168. Takagi T, Akasaka T, Yamamuro A et al (2000) Troglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with non-insulin dependent diabetes mellitus: a serial intravascular ultrasound study. J Am Coll Cardiol 36:1529–1535

    CAS  PubMed  Google Scholar 

  169. Costanzo MR, Naftel DC, Pritzker MR et al (1998) Heart transplant coronary artery disease detected by coronary angiography: a multiinstitutional study of preoperative donor and recipient risk factors. Cardiac Transplant Research Database. J Heart Lung Transplant 17:744–753

    CAS  PubMed  Google Scholar 

  170. Taylor DO, Edwards LB, Boucek MM et al (2006) Registry of the International Society for Heart and Lung Transplantation: twenty-third official adult heart transplantation report—2006. J Heart Lung Transplant 25:869–879

    PubMed  Google Scholar 

  171. Yeung AC, Davis SF, Hauptman PJ et al (1995) Incidence and progression of transplant coronary artery disease over 1 year: results of a multicenter trial with use of intravascular ultrasound. Multicenter Intravascular Ultrasound Transplant Study Group. J Heart Lung Transplant 14:S215–S220

    CAS  PubMed  Google Scholar 

  172. Libby P, Pober JS (2001) Chronic rejection. Immunity 14:387–397

    CAS  PubMed  Google Scholar 

  173. Salomon RN, Hughes CC, Schoen FJ et al (1991) Human coronary transplantation-associated arteriosclerosis. Evidence for a chronic immune reaction to activated graft endothelial cells. Am J Pathol 138:791–798

    CAS  PubMed  Google Scholar 

  174. Billingham ME (1992) Histopathology of graft coronary disease. J Heart Lung Transplant 11:S38–S44

    CAS  PubMed  Google Scholar 

  175. Mitchell RN (2009) Graft vascular disease: immune response meets the vessel wall. Annu Rev Pathol 4:19–47

    CAS  PubMed  Google Scholar 

  176. Kass M, Haddad H (2006) Cardiac allograft vasculopathy: pathology, prevention and treatment. Curr Opin Cardiol 21:132–137

    PubMed  Google Scholar 

  177. Valantine H, Rickenbacker P, Kemna M et al (2001) Metabolic abnormalities characteristic of dysmetabolic syndrome predict the development of transplant coronary artery disease: a prospective study. Circulation 103:2144–2152

    CAS  PubMed  Google Scholar 

  178. Kemna MS, Valantine HA, Hunt SA et al (1994) Metabolic risk factors for atherosclerosis in heart transplant recipients. Am Heart J 128:68–72

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. St. Boniface Hospital Research Centre, Winnipeg, MB, Canada

    Jennifer E. Enns, Carla G. Taylor & Peter Zahradka

  2. Canadian Centre for Agri-Food Research in Health and Medicine, Department of Physiology, University of Manitoba, Winnipeg, MB, Canada

    Jennifer E. Enns, Carla G. Taylor & Peter Zahradka

  3. Department of Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, Canada

    Carla G. Taylor & Peter Zahradka

  4. Molecular Physiology Laboratory, Canadian Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital Research Centre, 351 Tache Ave, Winnipeg, MB, R2H 2A6, Canada

    Peter Zahradka

Authors
  1. Jennifer E. Enns
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carla G. Taylor
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter Zahradka
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Peter Zahradka .

Editor information

Editors and Affiliations

  1. Department of Biophysics, University of Ankara, Ankara, Ankara, Turkey

    Belma Turan

  2. St. Boniface Hosp. Research, Univ. of Ma Institute of Cardiovascular Sciences, Winnipeg, Manitoba, Canada

    Naranjan S. Dhalla

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Science+Business Media New York

About this chapter

Cite this chapter

Enns, J.E., Taylor, C.G., Zahradka, P. (2014). The Role of Inflammation in Type 2 Diabetes-Driven Atherosclerosis. In: Turan, B., Dhalla, N. (eds) Diabetic Cardiomyopathy. Advances in Biochemistry in Health and Disease, vol 9. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-9317-4_13

Download citation

Publish with us

Policies and ethics

Search

Navigation