Periodontal pathogen Aggregatibacter actinomycetemcomitans deteriorates pressure overload-induced myocardial hypertrophy in mice.

Although a relationship between periodontitis and myocardial hypertrophy has been reported, the precise mechanism has not been clarified. The purpose of this study was to investigate the association between periodontal infection and myocardial hypertrophy. Transverse aortic constriction (TAC) was performed. Mice were injected with Aggregatibacter actinomycetemcomitans (A.a.) (0.1 mL of 10(8) CFU/mL) in the infected group and PBS in the control group. Echocardiography, histopathology, and immunohistochemistry were performed. Echocardiography indicated that left ventricular fractional shortening had decreased in the infected group compared to the control group on day 28. Heart to body weight ratio increased in the infected group compared to the control group. Histopathologically, A.a.-infected mice showed markedly enhanced cardiac hypertrophy, fibrosis and arteriosclerosis 4 weeks after TAC operation. Immunohistochemistry revealed that expression of MMP-2 in the interstitial tissue was enhanced in the infected group. These results suggested that the periodontal pathogen caused a deterioration of pressure overload-induced myocardial hypertrophy through MMP activation.

[1]  N. Frangogiannis,et al.  Characterization of the inflammatory and fibrotic response in a mouse model of cardiac pressure overload , 2009, Histochemistry and Cell Biology.

[2]  D. Tsiapras,et al.  Predictive value of B-type natriuretic peptides in detecting latent left ventricular diastolic dysfunction in beta-thalassemia major. , 2010, American heart journal.

[3]  V. Sambri,et al.  Major surface protein complex of Treponema denticola induces the production of tumor necrosis factor alpha, interleukin-1 beta, interleukin-6 and matrix metalloproteinase 9 by primary human peripheral blood monocytes. , 2010, Journal of periodontal research.

[4]  J. Salonen,et al.  Serum Antibody Levels to Actinobacillus actinomycetemcomitans Predict the Risk for Coronary Heart Disease , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[5]  C. Cutler,et al.  A novel mouse model to study the virulence of and host response to Porphyromonas (Bacteroides) gingivalis , 1991, Infection and immunity.

[6]  T. Salo,et al.  Matrix metalloproteinases: Contribution to pathogenesis, diagnosis and treatment of periodontal inflammation , 2006, Annals of medicine.

[7]  D. Gozdowski,et al.  Blood pressure and left ventricular mass in subjects with type 2 diabetes and gingivitis or chronic periodontitis. , 2010, Journal of clinical periodontology.

[8]  M. Jeong,et al.  Inhibition of Histone Deacetylation Blocks Cardiac Hypertrophy Induced by Angiotensin II Infusion and Aortic Banding , 2005, Circulation.

[9]  Douglas W Mahoney,et al.  Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. , 2003, JAMA.

[10]  K. Sunagawa,et al.  Targeted Deletion of Matrix Metalloproteinase 2 Ameliorates Myocardial Remodeling in Mice With Chronic Pressure Overload , 2006, Hypertension.

[11]  Chieh-Hsi Wu,et al.  Porphyromonas gingivalis-induced cellular hypertrophy and MMP-9 activity via different signaling pathways in H9c2 cardiomyoblast cells. , 2006, Journal of periodontology.

[12]  M. Radomski,et al.  Matrix metalloproteinase-2 contributes to ischemia-reperfusion injury in the heart. , 2000, Circulation.

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

[14]  P. Lucchesi,et al.  Extracellular matrix remodeling during the progression of volume overload-induced heart failure. , 2010, Journal of molecular and cellular cardiology.

[15]  Y. Huang,et al.  [Effects of losartan and simvastatin on collagen content, myocardial expression of MMP-2 mRNA, MMP-9 mRNA and TIMP-1 mRNA, TIMP-2 mRNA in pressure overload rat hearts]. , 2009, Zhonghua xin xue guan bing za zhi.

[16]  Saptarsi M. Haldar,et al.  Krüppel-like factor 4 regulates pressure-induced cardiac hypertrophy. , 2010, Journal of molecular and cellular cardiology.

[17]  F. Spinale,et al.  Matrix Metalloproteinase Inhibition Attenuates Left Ventricular Remodeling and Dysfunction in a Rat Model of Progressive Heart Failure , 2001, Circulation.

[18]  Y. Izumi,et al.  High incidence of actinobacillus actinomycetemcomitans infection in acute coronary syndrome. , 2007, International heart journal.

[19]  G. Roberts,et al.  Prevalence, intensity and nature of bacteraemia after toothbrushing. , 2008, Journal of dentistry.

[20]  Bruce J Paster,et al.  Bacteremia Associated With Toothbrushing and Dental Extraction , 2008, Circulation.

[21]  J. Penninger,et al.  Tumor necrosis factor induces matrix metalloproteinases in cardiomyocytes and cardiofibroblasts differentially via superoxide production in a PI3Kgamma-dependent manner. , 2010, American journal of physiology. Cell physiology.

[22]  P. Pavasant,et al.  Actinobacillus actinomycetemcomitans lipopolysaccharide activates matrix metalloproteinase-2 and increases receptor activator of nuclear factor-kappaB ligand expression in human periodontal ligament cells. , 2004, Journal of periodontology.

[23]  D. Kass,et al.  Sildenafil stops progressive chamber, cellular, and molecular remodeling and improves calcium handling and function in hearts with pre-existing advanced hypertrophy caused by pressure overload. , 2009, Journal of the American College of Cardiology.

[24]  P. Söder,et al.  Levels of matrix metalloproteinases-8 and -9 with simultaneous presence of periodontal pathogens in gingival crevicular fluid as well as matrix metalloproteinase-9 and cholesterol in blood. , 2006, Journal of periodontal research.

[25]  T. Salo,et al.  Matrix metalloproteinases (MMPs) in oral diseases. , 2004, Oral diseases.

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

[27]  Y. Izumi,et al.  Clarithromycin suppresses the periodontal bacteria-accelerated abdominal aortic aneurysms in mice. , 2012, Journal of periodontal research.

[28]  M. Kubo,et al.  Relationship between electrocardiographic abnormalities and periodontal disease: the Hisayama Study. , 2004, Journal of periodontology.

[29]  J. Karliner,et al.  Cardiac matrix metalloproteinase-2 expression independently induces marked ventricular remodeling and systolic dysfunction. , 2007, American journal of physiology. Heart and circulatory physiology.

[30]  I. Shiojima,et al.  Vascular Endothelial Growth Factor Blockade Promotes the Transition From Compensatory Cardiac Hypertrophy to Failure in Response to Pressure Overload , 2006, Hypertension.

[31]  B. Fernández,et al.  Ventricular function and natriuretic peptides in sequentially combined models of hypertension. , 2010, American journal of physiology. Heart and circulatory physiology.

[32]  G. Godeau,et al.  Expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in healthy and diseased human gingiva. , 2003, Journal of periodontology.

[33]  T. Salo,et al.  Local and Systemic Responses in Matrix Metalloproteinase 8-Deficient Mice during Porphyromonas gingivalis-Induced Periodontitis , 2008, Infection and Immunity.