[P2-3-04] Role of renin-angiotensin system for the development of cardiac disfunction in patients with periodontitis
Keywords:Porphyromonas gingivalis、心疾患、レニン-アンジオテンシン系
Role of renin-angiotensin system for the development of cardiac disfunction in patients with periodontitis
Chronic activation of renin-angiotensin system (RAS) is known to induce myocardial fibrosis and cardiac dysfunction. Captopril (Cap), ACE (Angiotensin Converting Enzyme) inhibitor that suppresses RAS activation, is widely used to treat hypertension and might protect heart from stresses. Systemic exposure to pro-inflammatory factors including lipopolysaccharide (LPS) derived from PG (Porphyromonas gingivalis) might contribute cardiovascular disease (CVD). We thus hypothesized that Porphyromonas gingivalis LPS (PG-LPS) might activate RAS, leading to cardiac dysfunction. Therefore, in this study, we evaluated cardiac function and cardiac remodeling in mice treated with PG-LPS at a dose equivalent to the circulating level in patients with periodontits. Mice were divided into 4 groups: 1) PBS (Control group), 2) PG-LPS (0.8mg/kg/day i.p. for 7 days), 3) Cap (via drinking water containing 0.1mg/ml), 4) Cap + PG-LPS. Serum angiotensin II (Ang II) as evaluated by ELISA was significantly increased in PG-LPS-treated mice (P<0.05), which was inhibited by Cap. Cardiac function, as evaluated by left ventricle ejection fraction and fractional shortening, was significantly decreased in PG-LPS-treated mice (P<0.001), which was inhibited by Cap. Cardiac fibrosis as evaluated by Masson-trichrome staining and cardiac myocyte apoptosis by TUNEL staining were significantly increased in PG-LPS-treated mice (P<0.001 each), which were inhibited again by Cap. Protein evaluation by Western blotting was in accordance with the results of physiological and histological experiments. These data suggest that periodontitis might cause cardiac dysfunction via activation of RAS.
Chronic activation of renin-angiotensin system (RAS) is known to induce myocardial fibrosis and cardiac dysfunction. Captopril (Cap), ACE (Angiotensin Converting Enzyme) inhibitor that suppresses RAS activation, is widely used to treat hypertension and might protect heart from stresses. Systemic exposure to pro-inflammatory factors including lipopolysaccharide (LPS) derived from PG (Porphyromonas gingivalis) might contribute cardiovascular disease (CVD). We thus hypothesized that Porphyromonas gingivalis LPS (PG-LPS) might activate RAS, leading to cardiac dysfunction. Therefore, in this study, we evaluated cardiac function and cardiac remodeling in mice treated with PG-LPS at a dose equivalent to the circulating level in patients with periodontits. Mice were divided into 4 groups: 1) PBS (Control group), 2) PG-LPS (0.8mg/kg/day i.p. for 7 days), 3) Cap (via drinking water containing 0.1mg/ml), 4) Cap + PG-LPS. Serum angiotensin II (Ang II) as evaluated by ELISA was significantly increased in PG-LPS-treated mice (P<0.05), which was inhibited by Cap. Cardiac function, as evaluated by left ventricle ejection fraction and fractional shortening, was significantly decreased in PG-LPS-treated mice (P<0.001), which was inhibited by Cap. Cardiac fibrosis as evaluated by Masson-trichrome staining and cardiac myocyte apoptosis by TUNEL staining were significantly increased in PG-LPS-treated mice (P<0.001 each), which were inhibited again by Cap. Protein evaluation by Western blotting was in accordance with the results of physiological and histological experiments. These data suggest that periodontitis might cause cardiac dysfunction via activation of RAS.