Periodontitis Accelerates Progression of Heart Failure With Preserved Ejection Fraction in Mice

Chronic low-grade inflammation and nitric oxide (NO) depletion are important contributors to heart failure with preserved ejection fraction (HFpEF) pathophysiology. Periodontitis (PD) is a common inflammatory disease implicated in dysregulation of NO hemostasis. Epidemiological studies have shown an association between PD and increased risk of cardiovascular disease, including heart failure. However, a causative relationship between the 2 diseases has not yet been proven. In this study, we sought to investigate the direct effect of PD induction on HFpEF progression in a mouse model. Induction of PD in HFpEF mice resulted in significant oral microbial dysbiosis, accelerated progression of diastolic dysfunction by echocardiography, and increased myocardial inflammation and fibrosis. These deleterious effects seen with PD were shown to be mediated by increased systemic blood pressure, increased systemic inflammation, and NO depletion. Our study provides evidence of potential mechanistic links between PD and HFpEF progression and suggests PD as a new therapeutic target for HFpEF.