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

J Oral Biosci. 2021 Dec;63(4):394-400. doi: 10.1016/j.job.2021.10.001. Epub 2021 Oct 29.

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.

Keywords: Apoptosis; Fibrosis; Heart failure; Lipopolysaccharides; Periodontitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / pharmacology
  • Heart Failure* / drug therapy
  • Humans
  • Lipopolysaccharides* / toxicity
  • Mice
  • Myocardium

Substances

  • Lipopolysaccharides
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2