Asuka Yoshida

Clarithromycin suppresses the periodontal bacteria-accelerated abdominal aortic aneurysms in mice.

BACKGROUND AND OBJECTIVE Although clarithromycin (CAM) has many biological functions, including regulation of MMPs, little is known about its effect on abdominal aortic aneurysms. Periodontopathic bacteria have been reported to be associated with several kinds of circulatory diseases. The purpose of this study was therefore to clarify the effect of CAM on periodontopathic bacteria-accelerated abdominal aortic aneurysms. MATERIAL AND METHODS Abdominal aortic aneurysm was produced in mice by the peri-aortic application of 0.25 m CaCl(2). The mice were inoculated once per week with live Porphyromonas gingivalis, which is one of the major periodontopathic bacteria. Test mice (n=8) were given a daily oral dose of CAM, while control mice (n=13) were not. RESULTS Four weeks after the operation, the P. gingivalis-injected and CAM-treated mice showed a significant decrease in the aortic diameter in comparison with the mice only injected with P. gingivalis. Histopathologically, the samples obtained from the P. gingivalis-injected and CAM-treated mice showed less elastic degradation. Moreover, the plasma MMP-2 concentration of the CAM-treated mice decreased significantly. CONCLUSION These findings suggest that CAM administration is useful to suppress periodontal bacteria-accelerated abdominal aortic aneurysms via MMP regulation.

Periodontitis and myocardial hypertrophy

There is a deep relationship between cardiovascular disease and periodontitis. It has been reported that myocardial hypertrophy may be affected by periodontitis in clinical settings. Although these clinical observations had some study limitations, they strongly suggest a direct association between severity of periodontitis and left ventricular hypertrophy. However, the detailed mechanisms between myocardial hypertrophy and periodontitis have not yet been elucidated. Recently, we demonstrated that periodontal bacteria infection is closely related to myocardial hypertrophy. In murine transverse aortic constriction models, a periodontal pathogen, Aggregatibacter actinomycetemcomitans markedly enhanced cardiac hypertrophy with matrix metalloproteinase-2 activation, while another pathogen Porphyromonas gingivalis (P.g.) did not accelerate these pathological changes. In the isoproterenol-induced myocardial hypertrophy model, P.g. induced myocardial hypertrophy through Toll-like receptor-2 signaling. From our results and other reports, regulation of chronic inflammation induced by periodontitis may have a key role in the treatment of myocardial hypertrophy. In this article, we review the pathophysiological mechanism between myocardial hypertrophy and periodontitis.

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.

Associations among tooth loss, systemic inflammation and antibody titers to periodontal pathogens in Japanese patients with cardiovascular disease

BACKGROUND AND OBJECTIVE It is well known that there is a strong relationship between periodontitis and cardiovascular disease (CVD). Tooth loss reflects an end-stage condition of oral diseases, such as periodontitis. Infection with specific periodontal pathogens is known as a possible factor that influences development of CVD. The aim of this study was to assess the relationship between the number of residual teeth and systemic inflammatory conditions in patients with CVD. MATERIAL AND METHODS We divided 364 patients with CVD into four groups, according to the number of residual teeth: (i) ≥20 teeth; (ii) 10-19 teeth; (iii) 1-9 teeth; and (iv) edentulous. We recorded medical history, blood data and periodontal conditions. Serum samples were obtained and their IgG titers against three major periodontal pathogens were measured. RESULTS Smoking rate and the prevalence of diabetes mellitus were higher in edentulous patients and in subjects with a few teeth compared with patients with many teeth. The levels of C-reactive protein were higher in patients with 1-9 teeth than in those with 10-19 teeth and with ≥20 teeth. The level of Porphyromonas gingivalis IgG in the group with 10-19 teeth was statistically higher than that in the group with ≥20 teeth. The level of P. gingivalis IgG in the edentulous group tended to be lower than that in the other groups. CONCLUSION The patients with 1-9 teeth had the highest level of C-reactive protein among the four groups, and the patients with 10-19 teeth had the highest level of IgG to periodontal bacteria. We conclude that the number of remaining teeth may be used to estimate the severity of systemic inflammation in patients with CVD.

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.