Effects of chronic Porphylomonas gingivalis lipopolysaccharide infusion on cardiac dysfunction in mice.

Abstract Objective Periodontitis (PD) is a chronic inflammatory disease of tooth-supportive tissue. An association between PD and cardiovascular disease (CVD) has been established. Although PD is generally accepted as a risk factor for CVD, the existence of a relationship remains debatable. Possible mechanisms include the release of inflammatory mediators such as lipopolysaccharide (LPS), which may spread systemically and promote CVD. Methods To compare the effects of lipopolysaccharide derived from Porphylomonas gingivalis (PG-LPS) on cardiac muscle in mice, mice were treated for 1 week with/without PG-LPS at a dose equivalent to the circulating level in PD patients (0.8 mg/kg/day). Results Cardiac function in terms of left ventricular ejection function was significantly decreased at 1 week compared to that in the control (from 66 ± 0.5% to 57 ± 1.1%). Compared to the controls, the number of apoptotic myocytes and the area of fibrosis were significantly increased by approximately 2.7-fold and 14-fold, respectively. The impairment of cardiac function appeared to involve the activation of cAMP/PKA signaling and cAMP/calmodulin kinase II signaling (CaMKII), leading to cardiac fibrosis, myocyte apoptosis and heart failure. Conclusions Our results indicate that cAMP/PKA and cAMP/CaMKII signaling may be a new therapeutic target for the treatment of cardiovascular diseases in patients with periodontitis.