Porphyromonas gingivalis Accelerates Neointimal Formation after Arterial Injury

Background: Inflammation plays a key role in neointimal hyperplasia after an arterial injury. Chronic infectious disorders, such as periodontitis, are associated with an increased risk of cardiovascular diseases. However, the effects of a periodontal infection on vascular remodeling have not been examined. We assess the hypothesis that periodontal infection could promote neointimal formation after an arterial injury. Methods: Mice were implanted with subcutaneous chambers (n = 41). Two weeks after implantation, the femoral arteries were injured, and Porphyromonas gingivalis (n = 21) or phosphate-buffered saline (n = 20) was injected into the chamber. The murine femoral arteries were obtained for the histopathological analysis. The expression level of mRNA in the femoral arteries was analyzed using quantitative reverse transcriptase polymerase chain reaction (n = 19–20). Results: The intima/media thickness ratio in the P. gingivalis infected group was found to be significantly increased in comparison to the non-infected group. The expression of matrix metalloproteinase-2 mRNA was significantly increased in the P. gingivalis infected group compared to the non-infected group. Conclusion: These findings demonstrate that P. gingivalis injection can promote neointimal formation after an arterial injury. Periodontitis may be a critical factor in the development of restenosis after arterial intervention.

[1]  Y. Houri-Haddad,et al.  Immunization to Porphyromonas gingivalis enhances the local pro-inflammatory response to subcutaneous bacterial challenge. , 2001, Journal of clinical periodontology.

[2]  J. Jones,et al.  Meta-analysis of periodontal disease and risk of coronary heart disease and stroke. , 2003, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[3]  J. Meurman,et al.  Oral health, atherosclerosis, and cardiovascular disease. , 2004, Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists.

[4]  M. Davies,et al.  Patterns of gelatinase activation induced by injury in the murine femoral artery. , 2009, The Journal of surgical research.

[5]  M. Makuuchi,et al.  A mouse model of vascular injury that induces rapid onset of medial cell apoptosis followed by reproducible neointimal hyperplasia. , 2000, Journal of molecular and cellular cardiology.

[6]  M. Davies,et al.  PATTERNS OF KINASE ACTIVATION INDUCED BY INJURY IN THE MURINE FEMORAL ARTERY , 2007, The Journal of surgical research.

[7]  F. C. Gibson,et al.  Innate Immune Recognition of Invasive Bacteria Accelerates Atherosclerosis in Apolipoprotein E–Deficient Mice , 2004, Circulation.

[8]  A. Matsumori,et al.  Anti-monocyte chemoattractant protein-1/monocyte chemotactic and activating factor antibody inhibits neointimal hyperplasia in injured rat carotid arteries. , 1999, Circulation research.

[9]  A. Progulske-Fox,et al.  Both the unique and repeat regions of the Porphyromonas gingivalis hemagglutin A are involved in adhesion and invasion of host cells. , 2012, Anaerobe.

[10]  Jason L Johnson,et al.  Matrix Metalloproteinase (MMP)-3 Activates MMP-9 Mediated Vascular Smooth Muscle Cell Migration and Neointima Formation in Mice , 2011, Arteriosclerosis, thrombosis, and vascular biology.

[11]  Porphyromonas gingivalis infection accelerates intimal thickening in iliac arteries in a balloon-injured rabbit model. , 2008, Journal of periodontology.

[12]  H. Kuramitsu,et al.  Induction of monocyte chemoattractant protein-1 by Porphyromonas gingivalis in human endothelial cells. , 2002, FEMS immunology and medical microbiology.

[13]  A. Griffen,et al.  Quantitative real-time PCR for Porphyromonas gingivalis and total bacteria. , 2000, Journal of clinical microbiology.

[14]  H. Jousimies-Somer,et al.  Bacteremia Following Surgical Dental Extraction with an Emphasis on Anaerobic Strains , 2004, Journal of dental research.

[15]  Y. Izumi,et al.  Porphyromonas gingivalis promotes murine abdominal aortic aneurysms via matrix metalloproteinase-2 induction. , 2011, Journal of periodontal research.

[16]  I. Olsen,et al.  Bacteremia in conjunction with endodontic therapy. , 1995, Endodontics & dental traumatology.

[17]  D. Grenier,et al.  Proteases of Porphyromonas gingivalis as important virulence factors in periodontal disease and potential targets for plant-derived compounds: a review article. , 2011, Current drug targets.

[18]  W. Stetler-Stevenson,et al.  Primate smooth muscle cell migration from aortic explants is mediated by endogenous platelet-derived growth factor and basic fibroblast growth factor acting through matrix metalloproteinases 2 and 9. , 1997, Circulation.

[19]  A. Sinusas,et al.  Matrix Metalloproteinase Activation Predicts Amelioration of Remodeling After Dietary Modification in Injured Arteries , 2011, Arteriosclerosis, thrombosis, and vascular biology.

[20]  J. Lessem,et al.  Periodontal infections cause changes in traditional and novel cardiovascular risk factors: results from a randomized controlled clinical trial. , 2006, American heart journal.

[21]  J. Bagg,et al.  Detection of bacteraemias during non-surgicalroot canal treatment. , 2005, Journal of dentistry.

[22]  M. Tonetti Periodontitis and risk for atherosclerosis: an update on intervention trials. , 2009, Journal of clinical periodontology.

[23]  M. Davies,et al.  ASSOCIATION FOR ACADEMIC SURGERY, 2008 Patterns of Gelatinase Activation Induced by Injury in the Murine Femoral Artery 1 , 2009 .

[24]  青山 典生 Porphyromonas gingivalis promotes murine abdominal aortic aneurysms via matrix metalloproteinase-2 induction , 2011 .

[25]  W. Lundergan,et al.  Longitudinal evaluation of GCF MMP-3 and TIMP-1 levels as prognostic factors for progression of periodontitis. , 2001, Journal of clinical periodontology.

[26]  Yuh-Yih Lin,et al.  Tissue Destruction Induced by Porphyromonas gingivalis Infection in a Mouse Chamber Model Is Associated with Host Tumor Necrosis Factor Generation , 2005, Infection and Immunity.

[27]  K. Chayama,et al.  Role of the Angiotensin II Type 2 Receptor in Arterial Remodeling after Wire Injury in Mice , 2008, Hypertension Research.

[28]  P. Söder,et al.  Detection and quantitation by lysis-filtration of bacteremia after different oral surgical procedures , 1990, Journal of clinical microbiology.

[29]  M. Isobe,et al.  Clarithromycin attenuates acute and chronic rejection via matrix metalloproteinase suppression in murine cardiac transplantation. , 2008, Journal of the American College of Cardiology.

[30]  E. L. Batista,et al.  Role for Periodontitis in the Progression of Lipid Deposition in an Animal Model , 2003, Infection and Immunity.

[31]  P. Libby,et al.  Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarction. , 2000, The Journal of clinical investigation.

[32]  A. Takeshita,et al.  Expression of monocyte chemoattractant protein 1 (MCP-1) in adult periodontal disease: increased monocyte chemotactic activity in crevicular fluids and induction of MCP-1 expression in gingival tissues , 1993, Infection and immunity.

[33]  Y. Taniyama,et al.  Ultrasound-Microbubble-Mediated NF-κB Decoy Transfection Attenuates Neointimal Formation after Arterial Injury in Mice , 2005, Journal of Vascular Research.

[34]  M. Isobe,et al.  The Mechanism of Anti-Inflammatory Effects of Prostaglandin E2 Receptor 4 Activation in Murine Cardiac Transplantation , 2009, Transplantation.

[35]  T. Schroeder,et al.  Identification of periodontal pathogens in atherosclerotic vessels. , 2005, Journal of periodontology.

[36]  D. Rothenbacher,et al.  Periodontal infections and coronary heart disease: role of periodontal bacteria and importance of total pathogen burden in the Coronary Event and Periodontal Disease (CORODONT) study. , 2006, Archives of internal medicine.

[37]  P. Söder,et al.  Matrix metalloproteinase-9 and tissue inhibitor of matrix metalloproteinase-1 in blood as markers for early atherosclerosis in subjects with chronic periodontitis. , 2009, Journal of periodontal research.

[38]  T. Warner,et al.  Monocyte chemotactic protein-1 expression is associated with the development of vein graft intimal hyperplasia. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[39]  T. Braun,et al.  Identification of pathogen and host-response markers correlated with periodontal disease. , 2009, Journal of periodontology.

[40]  H. Lijnen,et al.  Tissue inhibitor of matrix metalloproteinases-1 impairs arterial neointima formation after vascular injury in mice. , 1999, Circulation research.

[41]  C. K. Collings,et al.  Bacteremias following periodontal scaling in patients with healthy appearing gingiva. , 1967, Journal of periodontology.

[42]  P. Libby,et al.  Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. , 1994, The Journal of clinical investigation.

[43]  A. Itai,et al.  The effects of pharmacological PAI-1 inhibition on thrombus formation and neointima formation after arterial injury. , 2008, Expert opinion on therapeutic targets.

[44]  F. Chandad,et al.  Porphyromonas gingivalis‐induced inflammatory mediator profile in an ex vivo human whole blood model , 2006, Clinical and experimental immunology.

[45]  Z. Galis,et al.  Targeted Disruption of the Matrix Metalloproteinase-9 Gene Impairs Smooth Muscle Cell Migration and Geometrical Arterial Remodeling , 2002, Circulation research.

[46]  稲垣 裕 Ultrasound-microbubble-mediated NF-κB decoy transfection attenuates neointimal formation after arterial injury in mice , 2008 .

[47]  M. Trevisan,et al.  Identification of periodontal pathogens in atheromatous plaques. , 2000, Journal of periodontology.

[48]  J. Beck,et al.  Porphyromonas gingivalis Infection during Pregnancy Increases Maternal Tumor Necrosis Factor Alpha, Suppresses Maternal Interleukin-10, and Enhances Fetal Growth Restriction and Resorption in Mice , 2003, Infection and Immunity.

[49]  Z. Werb,et al.  Proteomic Identification of In Vivo Substrates for Matrix Metalloproteinases 2 and 9 Reveals a Mechanism for Resolution of Inflammation1 , 2006, The Journal of Immunology.

[50]  E. L. Batista,et al.  Porphyromonas gingivalis Infection Accelerates the Progression of Atherosclerosis in a Heterozygous Apolipoprotein E–Deficient Murine Model , 2002, Circulation.

[51]  M. Zile,et al.  Myocardial Infarct Expansion and Matrix Metalloproteinase Inhibition , 2003, Circulation.

[52]  L. Kesavalu,et al.  Virulence factors of Porphyromonas gingivalis. , 1999, Periodontology 2000.