Cardiovascular and Autonomic Dysfunction in Murine Ligature-Induced Periodontitis

Abstract

the present study examined the hemodynamics [arterial pressure (Ap), Ap variability (ApV), heart rate (HR), and heart rate variability (HRV)], cardiac function (echocardiographycally), and myocardial inflammation in Balb/c mice submitted to Periodontitis, through the ligation of the left first molar, or Sham surgical procedure. The first protocol indicated that the AP was similar (136 ± 2 vs. 132 ± 3 mmHg in Sham), while the HR was higher in mice with Periodontitis (475 ± 20 vs. 412 ± 18 bpm in Sham), compared to their Sham counterparts. The APV was higher in mice with Periodontitis when evaluated in the time domain (4.5 ± 0.3 vs. 3.4 ± 0.2 mmHg in Sham), frequency domain (power of the LF band of systolic AP), or through symbolic analysis (patterns 0V + 1V), indicating a sympathetic overactivity. The HRV was similar in the mice with Periodontitis, as compared to their Sham counterparts. In the second protocol, the mice with Periodontitis showed decreased cardiac output (10 ± 0.8 vs. 15 ± 1.4 mL/ min in Sham) and ejection fraction (37 ± 3 vs. 47 ± 2% in Sham) associated with increased myocardial cytokines (Interleukin-17, Interleukin-6, and Interleukin-4). This study shows that experimental periodontitis caused cardiac dysfunction, increased heart cytokines, and sympathetic overactivity, in line with epidemiological studies indicating an increased risk of cardiovascular events in clinical periodontitis. Periodontitis is caused by a chronic inflammatory response to a periodontal biofilm that deranges the supporting tissues around the teeth (alveolar bone, periodontal ligament, and cementum), causing dental loss 1. This inflammatory disease represents a major public health problem, with an estimated prevalence of over 790 million people worldwide 2,3. Of note, more than 700 species of bacteria are estimated in the oral cavity forming the dental biofilm 4,5. Biofilms can release biologically active products, including bacterial lipopolysaccharides, chemotactic mediators, protein toxins, and organic acids. These active products elicit different components of innate and adaptive immunity 6 followed by the production of inflammatory mediators, mainly cytokines produced by immune cells 7. These cytokines, including interleukin (IL)-17, IL-6, IL-4, and other inflammatory mediators, such as C-reactive protein, are released in response to the stimuli induced by the dental biofilm 8. Different rodent models of periodontal disease have been described to investigate the pathophysiology of this inflammatory disease and accompanying complications 9,10. Nevertheless, the placement of a ligature around a molar tooth is one of the most widely used model 11. Indeed, ligatures around the posterior teeth mimic human periodontitis, leading to local inflammatory cell accumulation, apical migration of junctional epithelium, and bone loss 9,12,13. Moreover, the structure of the dental gingival area in the rodent is quite similar to that exhibited by humans 14. Recent studies have proven that the harmful effects of periodontitis are not re...

Carotid sinus nerve stimulation attenuates alveolar bone loss and inflammation in experimental periodontitis

“…Moreover, there was no difference between baseline arterial pressure or HR between rats with and without periodontitis. Therefore, these data are in line with previous studies that demonstrated that ligature-induced periodontitis did not affect arterial pressure in mice 67 , and also that the CSN electrical stimulation did not change HR in unanesthetized rats 30 .…”

Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease

“…In a recent study by Ribeiro et al, on the influence of periodontitis on the cardiovascular system, a 4-0 sterile silk ligature was placed on the first molar of adult male Balb/c mice. The results showed increased levels of inflammatory cytokines in heart tissue, which led to sympathetic activity and cardiac dysfunction [113]. Two studies also reported changes in blood cell composition via the 5-0 ligature model using C57BL/6 mice.…”

“…As the influence on sympathetic activity has been reported [113], it is possible that periodontitis affects the whole nervous system due to blood circulation, including the brain. A previous study observed microgliosis and astrogliosis in the hippocampus during a range of 2-12 weeks of 5-0 ligature placement and indicated that the number of glial cells positively correlated with periodontal inflammation [117].…”

Short-term effect of ligature-induced periodontitis on cardiovascular variability and inflammatory response in spontaneously hypertensive rats

“…The jaws were stained with 1% methylene blue (1 g/100 mL, diluted water) for 5 min after the remove soft tissues in 9% hypochlorite for 5 h. Following, the steps and procedures were performed as previously described [22]. Briefly, a digital camera coupled into a D.F.…”

“…Moreover, a growing body of evidence has associated, epidemiologically, periodontal inflammation with cardiovascular diseases, such as arterial hypertension [21]. Our group recently demonstrated that periodontitis impacts the overall arterial pressure variability (APV) and cardiac performance, increases sympathetic activity and myocardial inflammation in Balb/c mice [22]. However, the effects of periodontitis in APV and HRV in hypertensive condition are not yet well established.…”