Abstract 13014: Porphyromonas Gingivalis, a Potent Periodontal Pathogen, Induces Cardiac Rupture After Myocardial Infarction in Mice
Introduction: Accumulating lines of evidence suggest that there is a strong association between periodontal disease and coronary artery diseases. However, the effects of periodontal disease on the pathophysiology of myocardial infarction (MI) remain unknown.
Hypothesis: Periodontal pathogens mediate detrimental effects on the infarcted myocardium.
Methods: C57BL/6J male mice were split into 3 groups. Before and after coronary artery ligation, each group was injected with one of the following bacteria or substance: Porphyromonas gingivalis (P.g.), Aggregatibacter actinomycetemcomitans (A.a.: a periodontal pathogen), or phosphate buffered saline (PBS). In vitro experiments were also conducted using cultured cardiomyocytes (CMs).
Results: Observation of the mice lasted for 14 days after MI. A significant increase of mortality, due to cardiac rupture, was observed on days 4 and 5 after MI in the P.g.-injected mice compared to the A.a.-injected or PBS-injected mice (P.g. [n=19] vs PBS [n=12] 42.1 vs 0%, p < 0.05, A.a. [n=7] vs PBS [n=12] 14.2 vs 0%). The release of H2O2 from the infarcted myocardium significantly increased in the P.g. group compared to the PBS group (P.g. [n=6] vs PBS [n=6]: 31.0 ± 9.1 vs 6.3 ± 3.4 pmol, p < 0.05). In the infarcted myocardium, the protein level of matrix metalloproteinase-9 (MMP-9), a protease which interrupts the healing process of damaged tissues, was significantly accumulated in the P.g. group (3.5 ± 0.9 fold, n=7) compared to the PBS group (n=7). Zymography revealed that MMP-9 activity was significantly higher in the P.g. group (2.9 ± 0.6 fold, n=7) than in the PBS group (n=7). These results suggest that infection with P.g. promotes production of H2O2, an enhancer of the MMP-9 activity, thereby aggravating the stability of the infarcted myocardium. In addition, the level of p18 Bax, an active form of Bax that strongly promotes apoptosis, significantly increased in the P.g. group (1.7 ± 0.1 fold, n=5) compared to the PBS group (n=5). Treatment with gingipain, a cysteine protease uniquely secreted from P.g., on cultured CMs promoted the accumulation of p18 Bax and CMs death.
Conclusions: Infection with P.g. during MI plays a detrimental role in the healing process of the myocardium, which in turn contributes to cardiac rupture.
Author Disclosures: Y. Shiheido: None. Y. Maejima: None. J. Suzuki: None. N. Aoyama: None. N. Kobayashi: None. M. Kaneko: None. Y. Izumi: None. M. Isobe: None.
- © 2014 by American Heart Association, Inc.