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Periodontitis and Atherosclerosis

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Studies on Periodontal Disease

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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.

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References

  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 95:559–569

    Article  PubMed  Google Scholar 

  2. Söder PO, Söder B, Nowak J, Jogestrand T (2005) Early carotid atherosclerosis in subjects with periodontal diseases. Stroke 36:1195–1200

    Article  PubMed  Google Scholar 

  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 356:911–920

    Article  CAS  PubMed  Google Scholar 

  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 35:465–472

    Article  CAS  PubMed  Google Scholar 

  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 83:690–698

    Article  PubMed  Google Scholar 

  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 89:879–902

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Bonomini F, Tengattini S, Fabiano A, Bianchi R, Rezzani R (2008) Atherosclerosis and oxidative stress. Histol Histopathol 23:381–390

    CAS  PubMed  Google Scholar 

  8. Lusis AJ (2000) Atherosclerosis. Nature 407:233–241

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  9. Bernhard D, Wang XL (2007) Smoking, oxidative stress and cardiovascular diseases—do anti-oxidative therapies fail? Curr Med Chem 14:1703–1712

    Article  CAS  PubMed  Google Scholar 

  10. Nicolls MR, Haskins K, Flores SC (2007) Oxidant stress, immune dysregulation, and vascular function in type I diabetes. Antioxid Redox Signal 9:879–889

    Article  CAS  PubMed  Google Scholar 

  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 24:994–998

    Article  PubMed  Google Scholar 

  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–H395

    Article  CAS  PubMed  Google Scholar 

  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 83:960–965

    Article  CAS  PubMed  Google Scholar 

  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 54:495–502

    Article  CAS  PubMed  Google Scholar 

  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 44:434–442

    Article  CAS  PubMed  Google Scholar 

  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 28:628–638

    Article  PubMed  Google Scholar 

  17. Mitra S, Goyal T, Mehta JL (2011) Oxidized LDL, LOX-1 and atherosclerosis. Cardiovasc Drugs Ther 25:419–429

    Article  CAS  PubMed  Google Scholar 

  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 80:810–818

    Article  CAS  PubMed  Google Scholar 

  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 87:5134–5138

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 344:254–257

    Article  CAS  PubMed  Google Scholar 

  21. McEver RP (1992) Leukocyte-endothelial cell interactions. Curr Opin Cell Biol 4:840–849

    Article  CAS  PubMed  Google Scholar 

  22. Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362:801–809

    Article  CAS  PubMed  Google Scholar 

  23. Madamanchi NR, Vendrov A, Runge MS (2005) Oxidative stress and vascular disease. Arterioscler Thromb Vasc Biol 25:29–38

    Article  CAS  PubMed  Google Scholar 

  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 80:1021–1032

    Google Scholar 

  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 78:2289–2302

    Article  PubMed  Google Scholar 

  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 23:2079–2086

    Article  PubMed Central  PubMed  Google Scholar 

  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 15:953–958

    Article  PubMed  Google Scholar 

  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 84:269–273

    Article  PubMed  Google Scholar 

  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 83:156–160

    Article  PubMed  Google Scholar 

  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 30:334–340

    Article  CAS  PubMed  Google Scholar 

  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 40:53–58

    Article  CAS  PubMed  Google Scholar 

  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 75:1694–1700

    Article  PubMed  Google Scholar 

  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 151:47

    Article  PubMed  Google Scholar 

  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 149:1050–1054

    Article  PubMed  Google Scholar 

  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 35:277–290

    Article  CAS  PubMed  Google Scholar 

  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 125:2520–2544

    Article  PubMed  Google Scholar 

  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 105:861–867

    Article  PubMed  Google Scholar 

  38. Gitlin JM, Loftin CD (2009) Cyclooxygenase-2 inhibition increases lipopolysaccharide-induced atherosclerosis in mice. Cardiovasc Res 81:400–407

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 23:1405–1411

    Article  CAS  PubMed  Google Scholar 

  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 40:378–384

    Article  CAS  PubMed  Google Scholar 

  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 59:131–136

    Article  CAS  PubMed  Google Scholar 

  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 39:4761–4768

    Article  Google Scholar 

  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 302:601–605

    Article  CAS  PubMed  Google Scholar 

  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 47:1227–1237

    Article  CAS  PubMed  Google Scholar 

  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 15:2988–3002

    Article  CAS  PubMed  Google Scholar 

  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 263:558–571

    Article  CAS  PubMed  Google Scholar 

  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 46:427–437

    Article  CAS  PubMed  Google Scholar 

  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):1615–1622

    Article  CAS  PubMed  Google Scholar 

  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 28:507–537

    Article  CAS  PubMed  Google Scholar 

  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 109:2109–2115

    Article  CAS  PubMed  Google Scholar 

  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 43:744–754

    Article  CAS  PubMed  Google Scholar 

  52. Ivanovski O, Nikolov IG, Drueke BT, Massy AZ (2007) Atherosclerosis and vascular calcification in uraemia: a new experimental model. Prilozi 28:11–24

    CAS  PubMed  Google Scholar 

  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 1783:1576–1584

    Article  Google Scholar 

  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 13:688–694

    Article  Google Scholar 

  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 377:1195–1198

    Article  CAS  PubMed  Google Scholar 

  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 38:1085–1090

    Article  CAS  PubMed  Google Scholar 

  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 44:51–58

    Article  CAS  PubMed  Google Scholar 

  58. Verhoye E, Langlois MR (2009) Circulating oxidized low-density lipoprotein: a biomarker of atherosclerosis and cardiovascular risk? Clin Chem Lab Med 47:128–137

    CAS  PubMed  Google Scholar 

  59. Steinhubl SR (2008) Why have antioxidants failed in clinical trials? Am J Cardiol 101:14D–19D

    Article  CAS  PubMed  Google Scholar 

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Acknowledgment

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

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Authors and Affiliations

  1. Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan

    Daisuke Ekuni, Takaaki Tomofuji & Manabu Morita

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  1. Daisuke Ekuni
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  2. Takaaki Tomofuji
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  3. Manabu Morita
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Correspondence to Daisuke Ekuni .

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Editors and Affiliations

  1. Department of Preventive Dentistry, Okayama University Graduate School of Medicine and Pharmaceutical Sciences, Okayama, Japan

    Daisuke Ekuni

  2. Dept of Science and Clinical Specialty Odontostomatology & Biochemistry, Polytechnical University of Marche Faculty of Medicine, Ancona, Italy

    Maurizio Battino

  3. Department of Preventive Dentistry, Okayama Univ Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama, Japan

    Takaaki Tomofuji

  4. Dept of Oral Biological & Medical Scienc Laboratory of Periodontal Biology, University of British Columbia Faculty of Dentistry, Vancouver, British Columbia, Canada

    Edward E. Putnins

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Ekuni, D., Tomofuji, T., Morita, M. (2014). Periodontitis and Atherosclerosis. In: Ekuni, D., Battino, M., Tomofuji, T., Putnins, E. (eds) Studies on Periodontal Disease. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4614-9557-4_13

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