Periodontal condition in Japanese coronary heart disease patients: A comparison between coronary and non-coronary heart diseases.

OBJECTIVE: The aim of this clinical trial was to assess the relationship between periodontal bacterial burden and coronary heart disease (CHD) in Japanese population. BACKGROUND: Many epidemiological reports suggest that periodontitis is a risk factor for CHD; however, the influence of each periodontal bacterium and periodontal condition in Japanese CHD patients is unclear. METHODS: We studied 897 patients with cardiovascular diseases in Tokyo Medical and Dental University Hospital from May 2012 to August 2015. The subjects were divided into six groups according to age and the existence of CHD (46-60 years with CHD (n = 56): Group YC, 61-70 years with CHD (n = 106): Group MC, over 70 years with CHD (n = 177): Group EC, 46-60 years without CHD (n = 152): Group YN, 61-70 years without CHD (n = 216): Group MN, and over 70 years without CHD (n = 190): Group EN). RESULTS: We found that the patients in Groups MC and EC had deeper periodontal pocket compared to the patients in Group YN (P < 0.05), although there was no statistical difference of pocket depth between Group YC and Groups MC and EC. Many subjects in Group EC had high anti-Porphyromonas gingivalis and anti-Prevotella intermedia antibodies in comparison to Group EN (P < 0.05). The CHD patients generally had worse oral condition than the non-CHD patients. Elderly with CHD had a higher level of serum anti-Porphyromonas gingivalis antibody and anti-Prevotella intermedia antibody than those without CHD. CONCLUSION: Increased periodontal infection was found in Japanese CHD patients compared to non-CHD patients.

Increased Oral Porphyromonas gingivalis Prevalence in Cardiovascular Patients with Uncontrolled Diabetes Mellitus.

The aim of this study was to determine the correlation between periodontopathic bacteria and diabetes mellitus (DM) status in cardiovascular disease (CVD) subjects.DM is associated with the progression of periodontitis. Several epidemiological studies have suggested that periodontitis may be a risk factor for CVD. However, no study has compared the periodontal condition between well-controlled and poorly-controlled DM patients with CVD.The subjects were well-controlled (n = 73) or poorly-controlled (n = 39) DM patients with CVD. Blood examinations and dental clinical measurements, including number of teeth, probing pocket depth, bleeding on probing (BOP), and clinical attachment level (CAL) were performed. Periodontopathic bacterial existence was evaluated.Worsened CAL and BOP rate were detected in the uncontrolled DM group compared to the controlled group. We found increased salivary Porphyromonas gingivalis counts in the uncontrolled DM group compared to well-controlled DM subjects.Specific periodontopathic bacterial infection may affect DM condition in CVD patients.

Japanese Cardiovascular Disease Patients with Diabetes Mellitus Suffer Increased Tooth Loss in Comparison to Those without Diabetes Mellitus -A Cross-sectional Study.

Objective Tooth loss is an irreversible condition that reflects the end-stage of oral diseases, including periodontitis. Although periodontitis is a major factor in the progression of diabetes mellitus (DM) and cardiovascular disease (CVD), no previous studies have compared tooth loss in CVD patients with and without DM. Methods The subjects included CVD patients with (n=94) and without (n=145) DM who attended Tokyo Medical and Dental University Hospital. Blood examinations and periodontal measurements were performed. Results The oral and periodontal examinations revealed that the numbers of missing teeth in the DM group were increased in comparison to the non-DM group. There was no significant difference between the groups with regard to the incidence of edentulism, the probing pocket depth, the clinical attachment level or the incidence of bleeding on probing. Conclusion We showed that the numbers of missing teeth among CVD patients with DM was significantly higher than that among CVD patients without DM.

Porphyromonas Gingivalis Elevated High-Mobility Group Box 1 Levels After Myocardial Infarction in Mice.

High mobility group box 1 (HMGB1) is a nuclear protein released from necrotic cells, inducing inflammatory responses. Epidemiological studies suggested a possible association between periodontitis and cardiovascular diseases (CVDs). Due to tissue damage and necrosis of cardiac cells following myocardial infarction (MI), HMGB1 is released, activating an inflammatory reaction. However, it remains unclear whether periodontitis is also involved in myocardial damage. The purpose of this study was to determine the effect of the periodontal pathogen Porphyromonas gingivalis (P.g.) after MI in mice.C57BL/6J wild type mice in post-MI were inoculated with P.g. in the infected group (P.g.-inoculated MI group) and with phosphate buffer saline (PBS) in the control group (PBS-injected MI group). Plasma samples and twelve tissue samples from mice hearts after MI were obtained. We determined the expression of HMGB1 by ELISA and immunohistochemistry.The level of HMGB1 protein in the P.g.-inoculated MI group was significantly higher than in the PBS-injected MI group on day 5, but not on day 14. Immunohistochemistry analysis revealed that HMGB1 was mainly expressed in cardiomyocytes, immune cells, and vascular endothelial cells in the PBS-injected MI group, while HMGB1 was seen broadly in degenerated cardiomyocytes, extracellular fields, immune cells, and vascular endothelial cells in the P.g.-inoculated MI group. A significant increase in the number of HMGB1 positive cells was observed in the P.g.-inoculated MI group compared to the PBS-injected MI group.Infection with P.g. after MI enhanced myocardial HMGB1 expression. There is a possible relationship between periodontitis and post-infarction myocardial inflammation through HMGB-1.

Detrimental effects of specific Periodontopathic bacterial infection on tachyarrhythmia compared to Bradyarrhythmia.

BACKGROUND: Tachyarrhythmia (TA) and bradyarrhythmia (BA) are cardiac rhythm disorders that result in the decline of quality of life. While patients with periodontitis are at a high risk of cardiovascular disease (CVD), little causal information between TA and BA has been provided to date. To assess the relationship, periodontal bacterial infection in patients with TA or BA was evaluated. METHODS: The subjects were patients with TA (n = 98) or BA (n = 40) who attended Tokyo Medical and Dental University hospital. Periodontal and blood examinations were performed. Periodontopathic bacterial existence in saliva was evaluated. RESULTS: We found that specific periodontopathic bacteria, Porphyromonas gingivalis and Prevotella intermedia, were highly detected in saliva from TA patients compared to BA subjects. The rates of hypertension and dyslipidemia were comparable between the two groups. CONCLUSION: Specific periodontal bacterial infection might affect TA progression.

Periodontitis deteriorates peripheral arterial disease in Japanese population via enhanced systemic inflammation.

Peripheral arterial disease (PAD) is a common manifestation of arterial stenosis of the extremity that reduces arterial flow. While patients with periodontitis are at a high risk of PAD, little causal information has been provided to date. To clarify the relationship, we conducted this cross-sectional study. The oral condition of patients with or without PAD, who attended Tokyo Medical and Dental University Hospital, was evaluated. Blood examinations and dental clinical measurements, including number of teeth, probing pocket depth (PPD), bleeding on probing (BOP) and clinical attachment level (CAL) were performed. Chi-square test was performed to compare gender, smoker rate, prevalence of DM, hypertension and dyslipidemia and edentulous rate. Wilcoxon test was used to compare bacterial counts and anti-bacterial antibodies and Student's t test was used to compare the other numerical values. The subjects were patients with (n = 34) or without (n = 956) PAD. We revealed that the PAD patients had more missing teeth (17.5 ± 11.0), a higher rate of edentulism (18%), and higher serum inflammatory factor levels than non-PAD patients (10.9 ± 8.7, 5%, respectively). On the other hand, there was no significant difference between hypertension, dyslipidemia, smoking status, HbA1c, bacterial antibody titers, and bacterial counts between the groups. In conclusion, we clarified that PAD patients had decreased tooth number and worsened oral and periodontal condition with enhanced systemic inflammation.

Toll-like receptor-2 has a critical role in periodontal pathogen-induced myocardial fibrosis in the pressure-overloaded murine hearts.

Recent studies have indicated that periodontopathic bacteria might accelerate the development of cardiac fibrosis. Porphyromonas gingivalis (P. gingivalis), a major periodontal bacterium, is mainly recognized by Toll-like receptor-2 (TLR-2). However, the role of TLR-2 in the acceleration of cardiac fibrosis via infections caused by periodontal bacteria has not yet been investigated. Here we investigated the role TLR-2 has in periodontal pathogen-induced cardiac fibrosis. TLR-2 knockout (KO) and wild type (WT) male C57BL/6 mice were subjected to a transverse aortic constriction (TAC) surgical procedure 2 weeks after chamber implantation. After the TAC operation, mice received injections once a week of P. gingivalis or vehicle into the chambers that were implanted in the back of mice. Fractional shortening (FS) was measured using echocardiography 1 week after the TAC surgical procedure. Four weeks after the TAC surgical procedure, blood and heart samples were collected. FS in the infected group of WT mice was significantly lower than in mice that received sham operations; however, FS in the uninfected group did not decrease in a similar manner to that in the infected group. Cardiac fibrosis was significantly enhanced in TAC-operated WT mice infected with P. gingivalis (n=14), whereas it was inhibited in TAC-operated TLR-2 KO mice infected with P. gingivalis (n=7). The level of matrix metalloproteinase-2 (MMP-2) mRNA was higher in WT mice infected with P. gingivalis compared with non-infected WT mice. However, the level of MMP-2 mRNA was significantly lower in TLR-2 KO mice compared with that in WT mice. In conclusion, TLR-2 had a critical role in the development of cardiac fibrosis under the conditions of pressure overload and periodontal pathogen infection.

A Periodontal pathogen Porphyromonas gingivalis deteriorates Isoproterenol-Induced myocardial remodeling in mice.

Heart failure is a serious disease induced by several conditions, including hypertrophic cardiomyopathy. Although many reports suggest that there is an association between periodontal disease and cardiovascular disease, the mechanisms have yet to be elucidated. The purpose of this study was to clarify the relationship between periodontal disease and heart disease, especially in cardiac hypertrophy. We used C57BL/6J mice and implanted two types of subcutaneous chambers. First, we subcutaneously implanted a coil-shaped chamber into the back of a mouse. Porphyromonas gingivalis (P.g.), a major periodontal pathogen, was injected into the chamber. Then, an osmotic pump was implanted to infuse isoproterenol. Four weeks after the ISO infusion, we performed echocardiography and harvested the heart and blood. We measured the serum level of anti-P.g.-IgG using ELISA. The mRNA levels of several factors were measured using PCR. We found stronger cardiomyocyte hypertrophy in the ISO(+)/P.g.(+) mice compared with the ISO(+)/P.g.(-) mice. The total square of randomly selected cardiomyocytes was 23% larger in the ISO(+)/P.g.(+) mice than in the ISO(+)/P.g.(-) mice. We detected a higher level of mRNA expression in Toll-like receptor 2 and NADPH oxidase 4 in the ISO(+)/P.g.(-) mice compared with the control group. We revealed that a periodontal pathogen affected ISO-induced cardiac hypertrophy via oxidative stress.

Porphyromonas gingivalis, a periodontal pathogen, enhances myocardial vulnerability, thereby promoting post-infarct cardiac rupture.

There is a strong association between periodontal disease (PD) and atherosclerosis. However, it remains unknown whether PD is also involved in myocardial damage. We hypothesized that infection with periodontal pathogens could cause an adverse outcome after myocardial infarction (MI). C57BL/6J mice were inoculated with Porphyromonas gingivalis (P.g.), a major periodontal pathogen, or injected with phosphate-buffered saline (PBS) into a subcutaneously-implanted steelcoil chamber before and after coronary artery ligation. A significant increase in mortality, due to cardiac rupture, was observed in the P.g.-inoculated MI mice. Ultrastructural examinations revealed that P.g. invaded the ischemic myocardium of the P.g.-inoculated MI mice. The expression of p18 Bax, an active form of pro-apoptotic Bax protein, markedly increased in the P.g.-inoculated MI hearts. In vitro experiments demonstrated that gingipain, a protease uniquely secreted from P.g., cleaved wild type Bax at Arg34, as evidenced by the observation that the cleavage of Bax by gingipain was completely abolished by the Arg34Ala mutation in Bax. Treatment with immunoglobulin Y against gingipain significantly decreased the mortality of the P.g.-inoculated MI mice caused by cardiac rupture. Furthermore, inoculation of P.g. also resulted in an increase of MMP-9 activity in the post-MI myocardium by enhancing oxidative stress, possibly through impairing the selective autophagy-mediated clearance of damaged mitochondria. In conclusion, infection with P.g. during MI plays a detrimental role in the healing process of the infarcted myocardium by invasion of P.g. into the myocardium, thereby promoting apoptosis and the MMP-9 activity of the myocardium, which, in turn, causes cardiac rupture.