Advertisement

Periodontitis and Atherosclerosis

  • Daisuke Ekuni
  • Takaaki Tomofuji
  • Manabu Morita
Chapter
Part of the Oxidative Stress in Applied Basic Research and Clinical Practice book series (OXISTRESS)

Abstract

In this chapter, we summarize the relationship between periodontitis and atherosclerosis and the involvement of oxidative stress. Several studies indicate that reactive oxygen and nitrogen species have a causal role in atherosclerosis. Periodontitis is one of the most widespread inflammatory diseases, and it induces excessive production of reactive oxygen species in periodontal lesions. Previous studies have suggested that there is an association between cardiovascular disease (CVD) and periodontitis, and that periodontitis plays an etiological role in CVD, including atherosclerosis. Two prevailing hypotheses may explain the relationship between periodontitis and CVD. First, periodontal bacteria may have a direct effect on the vasculature. Second, local inflammation causes an enhanced inflammatory response at distant sites without the spread of the infectious agent. We focused on the second hypothesis because oxidative stress by periodontitis may be an initiating or promoting factor leading to inflammatory injury in the pathogenesis of atherosclerosis. The role of antioxidants in controlling periodontitis and atherosclerosis is also discussed.

Keywords

Reactive Oxygen Species Inflammatory Injury Periodontitis Group Human Periodontitis Nitrotyrosine Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgment

We are grateful to Dr. Noriko Takeuchi (Okayama University, Okayama, Japan) for help creating figures.

References

  1. 1.
    Janket SJ, Baird AE, Chuang SK, Jones JA (2003) Meta-analysis of periodontal disease and risk of coronary heart disease and stroke. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 95:559–569PubMedCrossRefGoogle Scholar
  2. 2.
    Söder PO, Söder B, Nowak J, Jogestrand T (2005) Early carotid atherosclerosis in subjects with periodontal diseases. Stroke 36:1195–1200PubMedCrossRefGoogle Scholar
  3. 3.
    Tonetti MS, D’Aiuto F, Nibali L, Donald A, Storry C, Parkar M, Suvan J, Hingorani AD, Vallance P, Deanfield J (2007) Treatment of periodontitis and endothelial function. N Engl J Med 356:911–920PubMedCrossRefGoogle Scholar
  4. 4.
    Cairo F, Castellani S, Gori AM, Nieri M, Baldelli G, Abbate R, Pini-Prato GP (2008) Severe periodontitis in young adults is associated with sub-clinical atherosclerosis. J Clin Periodontol 35:465–472PubMedCrossRefGoogle Scholar
  5. 5.
    López-Jornet P, Berná-Mestre JD, Berná-Serna JD, Camacho-Alonso F, Fernandez-Millan S, Reus-Pintado M (2011) Measurement of atherosclerosis markers in patients with periodontitis: a case-control study. J Periodontol 83:690–698PubMedCrossRefGoogle Scholar
  6. 6.
    Kebschull M, Demmer RT, Papapanou PN (2010) “Gum bug, leave my heart alone!”—epidemiologic and mechanistic evidence linking periodontal infections and atherosclerosis. J Dent Res 89:879–902PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Bonomini F, Tengattini S, Fabiano A, Bianchi R, Rezzani R (2008) Atherosclerosis and oxidative stress. Histol Histopathol 23:381–390PubMedGoogle Scholar
  8. 8.
    Lusis AJ (2000) Atherosclerosis. Nature 407:233–241PubMedCentralPubMedCrossRefGoogle Scholar
  9. 9.
    Bernhard D, Wang XL (2007) Smoking, oxidative stress and cardiovascular diseases—do anti-oxidative therapies fail? Curr Med Chem 14:1703–1712PubMedCrossRefGoogle Scholar
  10. 10.
    Nicolls MR, Haskins K, Flores SC (2007) Oxidant stress, immune dysregulation, and vascular function in type I diabetes. Antioxid Redox Signal 9:879–889PubMedCrossRefGoogle Scholar
  11. 11.
    Mügge A, Brandes RP, Böger RH, Dwenger A, Bode-Böger S, Kienke S, Frölich JC, Lichtlen PR (1994) Vascular release of superoxide radicals is enhanced in hypercholesterolemic rabbits. J Cardiovasc Pharmacol 24:994–998PubMedCrossRefGoogle Scholar
  12. 12.
    Buday A, Orsy P, Godó M, Mózes M, Kökény G, Lacza Z, Koller A, Ungvári Z, Gross ML, Benyó Z, Hamar P (2010) Elevated systemic TGF-beta impairs aortic vasomotor function through activation of NADPH oxidase-driven superoxide production and leads to hypertension, myocardial remodeling and increased plaque formation in apoE(−/−) mice. Am J Physiol Heart Circ Physiol 299:H386–H395PubMedCrossRefGoogle Scholar
  13. 13.
    Huang A, Sun D, Kaley G, Koller A (1998) Superoxide released to high intra-arteriolar pressure reduces nitric oxide-mediated shear stress- and agonist-induced dilations. Circ Res 83:960–965PubMedCrossRefGoogle Scholar
  14. 14.
    Ekuni D, Tomofuji T, Sanbe T, Irie K, Azuma T, Maruyama T, Tamaki N, Murakami J, Kokeguchi S, Yamamoto T (2009) Vitamin C intake attenuates the degree of experimental atherosclerosis induced by periodontitis in the rat by decreasing oxidative stress. Arch Oral Biol 54:495–502PubMedCrossRefGoogle Scholar
  15. 15.
    Ekuni D, Tomofuji T, Sanbe T, Irie K, Azuma T, Maruyama T, Tamaki N, Murakami J, Kokeguchi S, Yamamoto T (2009) Periodontitis-induced lipid peroxidation in rat descending aorta is involved in the initiation of atherosclerosis. J Periodontal Res 44:434–442PubMedCrossRefGoogle Scholar
  16. 16.
    Antoniades C, Tousoulis D, Tentolouris C, Toutouzas P, Stefanadis C (2003) Oxidative stress, antioxidant vitamins, and atherosclerosis. From basic research to clinical practice. Herz 28:628–638PubMedCrossRefGoogle Scholar
  17. 17.
    Mitra S, Goyal T, Mehta JL (2011) Oxidized LDL, LOX-1 and atherosclerosis. Cardiovasc Drugs Ther 25:419–429PubMedCrossRefGoogle Scholar
  18. 18.
    Vora DK, Fang ZT, Liva SM, Tyner TR, Parhami F, Watson AD, Drake TA, Territo MC, Berliner JA (1997) Induction of P-selectin by oxidized lipoproteins. Separate effects on synthesis and surface expression. Circ Res 80:810–818PubMedCrossRefGoogle Scholar
  19. 19.
    Cushing SD, Berliner JA, Valente AJ, Territo MC, Navab M, Parhami F, Gerrity R, Schwartz CJ, Fogelman AM (1990) Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells. Proc Natl Acad Sci U S A 87:5134–5138PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Rajavashisth TB, Andalibi A, Territo MC, Berliner JA, Navab M, Fogelman AM, Lusis AJ (1990) Induction of endothelial cell expression of granulocyte and macrophage colony-stimulating factors by modified low-density lipoproteins. Nature 344:254–257PubMedCrossRefGoogle Scholar
  21. 21.
    McEver RP (1992) Leukocyte-endothelial cell interactions. Curr Opin Cell Biol 4:840–849PubMedCrossRefGoogle Scholar
  22. 22.
    Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362:801–809PubMedCrossRefGoogle Scholar
  23. 23.
    Madamanchi NR, Vendrov A, Runge MS (2005) Oxidative stress and vascular disease. Arterioscler Thromb Vasc Biol 25:29–38PubMedCrossRefGoogle Scholar
  24. 24.
    Friedewald VE, Kornman KS, Beck JD, Genco R, Goldfine A, Libby P, Offenbacher S, Ridker PM, Van Dyke TE, Roberts WC, American Journal of Cardiology, Journal of Periodontology (2009) The American Journal of Cardiology and Journal of Periodontology editors’ consensus: periodontitis and atherosclerotic cardiovascular disease. J Periodontol 80:1021–1032Google Scholar
  25. 25.
    Mustapha IZ, Debrey S, Oladubu M, Ugarte R (2007) Markers of systemic bacterial exposure in periodontal disease and cardiovascular disease risk: a systematic review and meta-analysis. J Periodontol 78:2289–2302PubMedCrossRefGoogle Scholar
  26. 26.
    Humphrey LL, Fu R, Buckley DI, Freeman M, Helfand M (2008) Periodontal disease and coronary heart disease incidence: a systematic review and meta-analysis. J Gen Intern Med 23:2079–2086PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Tamaki N, Tomofuji T, Ekuni D, Yamanaka R, Morita M (2011) Periodontal treatment decreases plasma oxidized LDL level and oxidative stress. Clin Oral Investig 15:953–958PubMedCrossRefGoogle Scholar
  28. 28.
    D’Aiuto F, Nibali L, Parkar M, Suvan J, Tonetti MS (2005) Short-term effects of intensive periodontal therapy on serum inflammatory markers and cholesterol. J Dent Res 84:269–273PubMedCrossRefGoogle Scholar
  29. 29.
    D’Aiuto F, Parkar M, Andreou G, Suvan J, Brett PM, Ready D, Tonetti MS (2004) Periodontitis and systemic inflammation: control of the local infection is associated with a reduction in serum inflammatory markers. J Dent Res 83:156–160PubMedCrossRefGoogle Scholar
  30. 30.
    Ide M, McPartlin D, Coward PY, Crook M, Lumb P, Wilson RF (2003) Effect of treatment of chronic periodontitis on levels of serum markers of acute-phase inflammatory and vascular responses. J Clin Periodontol 30:334–340PubMedCrossRefGoogle Scholar
  31. 31.
    Yamazaki K, Honda T, Oda T, Ueki-Maruyama K, Nakajima T, Yoshie H, Seymour GJ (2005) Effect of periodontal treatment on the C-reactive protein and proinflammatory cytokine levels in Japanese periodontitis patients. J Periodontal Res 40:53–58PubMedCrossRefGoogle Scholar
  32. 32.
    Mercanoglu F, Oflaz H, Oz O, Gökbuget AY, Genchellac H, Sezer M, Nişanci Y, Umman S (2004) Endothelial dysfunction in patients with chronic periodontitis and its improvement after initial periodontal therapy. J Periodontol 75:1694–1700PubMedCrossRefGoogle Scholar
  33. 33.
    Elter JR, Hinderliter AL, Offenbacher S, Beck JD, Caughey M, Brodala N, Madianos PN (2006) The effects of periodontal therapy on vascular endothelial function: a pilot trial. Am Heart J 151:47PubMedCrossRefGoogle Scholar
  34. 34.
    Seinost G, Wimmer G, Skerget M, Thaller E, Brodmann M, Gasser R, Bratschko RO, Pilger E (2005) Periodontal treatment improves endothelial dysfunction in patients with severe periodontitis. Am Heart J 149:1050–1054PubMedCrossRefGoogle Scholar
  35. 35.
    Paraskevas S, Huizinga JD, Loos BG (2008) A systematic review and meta-analyses on C-reactive protein in relation to periodontitis. J Clin Periodontol 35:277–290PubMedCrossRefGoogle Scholar
  36. 36.
    Lockhart PB, Bolger AF, Papapanou PN, Osinbowale O, Trevisan M, Levison ME, Taubert KA, Newburger JW, Gornik HL, Gewitz MH, Wilson WR, Smith SC Jr, Baddour LM (2012) Periodontal disease and atherosclerotic vascular disease: does the evidence support an independent association? A scientific statement from the American Heart Association. Circulation 125:2520–2544PubMedCrossRefGoogle Scholar
  37. 37.
    Li L, Messas E, Batista EL Jr, Levine RA, Amar S (2002) Porphyromonas gingivalis infection accelerates the progression of atherosclerosis in a heterozygous apolipoprotein E-deficient murine model. Circulation 105:861–867PubMedCrossRefGoogle Scholar
  38. 38.
    Gitlin JM, Loftin CD (2009) Cyclooxygenase-2 inhibition increases lipopolysaccharide-induced atherosclerosis in mice. Cardiovasc Res 81:400–407PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Lalla E, Lamster IB, Hofmann MA, Bucciarelli L, Jerud AP, Tucker S, Lu Y, Papapanou PN, Schmidt AM (2003) Oral infection with a periodontal pathogen accelerates early atherosclerosis in apolipoprotein E-null mice. Arterioscler Thromb Vasc Biol 23:1405–1411PubMedCrossRefGoogle Scholar
  40. 40.
    Tsai CC, Chen HS, Chen SL, Ho YP, Ho KY, Wu YM, Hung CC (2005) Lipid peroxidation: a possible role in the induction and progression of chronic periodontitis. J Periodontal Res 40:378–384PubMedCrossRefGoogle Scholar
  41. 41.
    Hermans N, Cos P, De Meyer GR, Maes L, Pieters L, Vanden Berghe D, Vlietinck AJ, De Bruyne T (2007) Study of potential systemic oxidative stress animal models for the evaluation of antioxidant activity: status of lipid peroxidation and fat-soluble antioxidants. J Pharm Pharmacol 59:131–136PubMedCrossRefGoogle Scholar
  42. 42.
    Pouliot M, Clish CB, Petasis NA, Van Dyke TE, Serhan CN (2002) Lipoxin A(4) analogues inhibit leukocyte recruitment to Porphyromonas gingivalis: a role for cyclooxygenase-2 and lipoxins in periodontal disease. Biochemistry 39:4761–4768CrossRefGoogle Scholar
  43. 43.
    Li D, Chen H, Romeo F, Sawamura T, Saldeen T, Mehta JL (2002) Statins modulate oxidized low-density lipoprotein-mediated adhesion molecule expression in human coronary artery endothelial cells: role of LOX-1. J Pharmacol Exp Ther 302:601–605PubMedCrossRefGoogle Scholar
  44. 44.
    Ma FX, Zhou B, Chen Z, Ren Q, Lu SH, Sawamura T, Han ZC (2006) Oxidized low density lipoprotein impairs endothelial progenitor cells by regulation of endothelial nitric oxide synthase. J Lipid Res 47:1227–1237PubMedCrossRefGoogle Scholar
  45. 45.
    Victor VM, Rocha M, Sola E, Banuls C, Garcia-Malpartida K, Hernandez-Mijares A (2009) Oxidative stress, endothelial dysfunction and atherosclerosis. Curr Pharm Des 15:2988–3002PubMedCrossRefGoogle Scholar
  46. 46.
    Bengtsson T, Karlsson H, Gunnarsson P, Skoglund C, Elison C, Leanderson P, Lindahl M (2008) The periodontal pathogen Porphyromonas gingivalis cleaves apoB-100 and increases the expression of apoM in LDL in whole blood leading to cell proliferation. J Intern Med 263:558–571PubMedCrossRefGoogle Scholar
  47. 47.
    Lei L, Li H, Yan F, Li Y, Xiao Y (2011) Porphyromonas gingivalis lipopolysaccharide alters atherosclerotic-related gene expression in oxidized low-density-lipoprotein-induced macrophages and foam cells. J Periodontal Res 46:427–437PubMedCrossRefGoogle Scholar
  48. 48.
    Ekuni D, Tomofuji T, Endo Y, Kasuyama K, Irie K, Azuma T, Tamaki N, Mizutani S, Kojima A, Morita M (2012) Hydrogen-rich water prevents lipid deposition in the descending aorta in a rat periodontitis model. Arch Oral Biol 57(12):1615–1622PubMedCrossRefGoogle Scholar
  49. 49.
    Villacorta L, Azzi A, Zingg JM (2007) Regulatory role of vitamins E and C on extracellular matrix components of the vascular system. Mol Aspects Med 28:507–537PubMedCrossRefGoogle Scholar
  50. 50.
    Zhu XY, Rodriguez-Porcel M, Bentley MD, Chade AR, Sica V, Napoli C, Caplice N, Ritman EL, Lerman A, Lerman LO (2004) Antioxidant intervention attenuates myocardial neovascularization in hypercholesterolemia. Circulation 109:2109–2115PubMedCrossRefGoogle Scholar
  51. 51.
    Cromheeke KM, Kockx MM, De Meyer GR, Bosmans JM, Bult H, Beelaerts WJ, Vrints CJ, Herman AG (1999) Inducible nitric oxide synthase colocalizes with signs of lipid oxidation/peroxidation in human atherosclerotic plaques. Cardiovasc Res 43:744–754PubMedCrossRefGoogle Scholar
  52. 52.
    Ivanovski O, Nikolov IG, Drueke BT, Massy AZ (2007) Atherosclerosis and vascular calcification in uraemia: a new experimental model. Prilozi 28:11–24PubMedGoogle Scholar
  53. 53.
    Mu H, Wang X, Lin P, Yao Q, Chen C (1990) Nitrotyrosine promotes human aortic smooth muscle cell migration through oxidative stress and ERK1/2 activation. Biochim Biophys Acta 1783:1576–1584CrossRefGoogle Scholar
  54. 54.
    Ohsawa I, Ishikawa M, Takahashi K, Watanabe M, Nishimaki K, Yamagata K, Katsura K, Katayama Y, Asoh S, Ohta S (1990) Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat Med 13:688–694CrossRefGoogle Scholar
  55. 55.
    Ohsawa I, Nishimaki K, Yamagata K, Ishikawa M, Ohta S (2008) Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice. Biochem Biophys Res Commun 377:1195–1198PubMedCrossRefGoogle Scholar
  56. 56.
    Kasuyama K, Tomofuji T, Ekuni D, Tamaki N, Azuma T, Irie K, Endo Y, Morita M (2011) Hydrogen-rich water attenuates experimental periodontitis in a rat model. J Clin Periodontol 38:1085–1090PubMedCrossRefGoogle Scholar
  57. 57.
    Choi EK, Park SA, Oh WM, Kang HC, Kuramitsu HK, Kim BG, Kang IC (2005) Mechanisms of Porphyromonas gingivalis-induced monocyte chemoattractant protein-1 expression in endothelial cells. FEMS Immunol Med Microbiol 44:51–58PubMedCrossRefGoogle Scholar
  58. 58.
    Verhoye E, Langlois MR (2009) Circulating oxidized low-density lipoprotein: a biomarker of atherosclerosis and cardiovascular risk? Clin Chem Lab Med 47:128–137PubMedGoogle Scholar
  59. 59.
    Steinhubl SR (2008) Why have antioxidants failed in clinical trials? Am J Cardiol 101:14D–19DPubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Daisuke Ekuni
    • 1
  • Takaaki Tomofuji
    • 1
  • Manabu Morita
    • 1
  1. 1.Department of Preventive DentistryOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesKita-kuJapan

Personalised recommendations