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Periodontitis induces endothelial dysfunction in mice.

ABSTRACT: The treatment of periodontitis has numerous positive effects on established chronic health conditions, including cardiovascular disease and diabetes. However, ethical considerations do limit the establishment of human trials to investigate whether periodontitis promotes the early stages of chronic conditions. Therefore, the aim of this study was to investigate whether periodontitis induces endothelial dysfunction in hyperlipidemic apolipoprotein E gene-deficient (ApoE^-/-) mice. Forty-five 8-week-old ApoE^-/- mice were challenged by oral lavage with Porphyromonas gingivalis and Streptococcus gordonii for 4 weeks. A subgroup of animals (n = 15-17/group) was placed in a metabolic chamber immediately before euthanasia at 4 weeks to measure VO₂/CO₂ concentrations and voluntary locomotion. In infected and control animals alveolar bone levels were measured by x-ray imaging and endothelial function was determined by measuring endothelial-dependent vasorelaxation of aortic rings. The mRNA expression levels of serum amyloid A and tumor necrosis factor were determined in liver tissues by qRT PCR and protein concentrations in serum by ELISA. Caecal contents were analysed by sequencing to determine changes to the gut microbiota to investigate linkages between microbiome and systemic changes. The results showed that oral lavage of P. gingivalis and S. gordonii for 4 weeks, initiated periodontitis in ApoE^-/- mice, similar to the human situation. The oral inflammation was accompanied by a significant increase in mRNA expression of pro-inflammatory mediators serum amyloid A1 and tumor necrosis factor in the liver. Mice with periodontitis also exhibited impaired endothelial-dependent vasorelaxation responses to acetylcholine. This systemic response was connected to increased energy expenditure, locomotion and respiratory quotient. No differences were detected in caecal microbiota between the infected and control animals. Overall, this is the first report that provide evidence that periodontitis induces endothelial dysfunction in mice. Other systemic responses observed in response to the local reaction need further investigation. The study suggests that early prevention of periodontitis may help limit the early stages of endothelial dysfunction that is linked to atherogenesis in humans.

SUBMITTER: Parvaneh M

PROVIDER: S-EPMC8298548 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:A large body of evidence underlines an association between periodontal disease and cardiovascular disease. In contrast, data on its relation with endothelial dysfunction as a marker of early subclinical atherosclerosis is inconclusive and limited to patient-cohort studies. We therefore investigated the association between periodontal disease and flow-mediated dilation of the brachial artery (FMD) as a measure of endothelial dysfunction in a general population, and also addressed a possible mediation via inflammation. The study population comprised 1,234 subjects (50.5% men) aged 25-85 years from the 5-year follow-up of the Study of Health in Pomerania, a population-based cohort study. Clinical attachment loss (CAL) and pocket probing depth (PPD) as measures of periodontal disease were assessed half-mouth at four sites per tooth. Subjects were classified according to the periodontitis case definition proposed by Tonetti and Claffey (2005). Measurements of FMD and nitroglycerin-mediated dilation (NMD) were performed using standardized ultrasound techniques. High-sensitive C-reactive protein, fibrinogen and leukocyte count were measured. Fully adjusted multivariate linear regression analyses revealed significant associations of the percentage of sites with PPD ≥ 6 mm with FMD (p(trend)=0.048), with subjects within the highest category having a 0.74% higher FMD compared to subjects within the lowest category (p<0.05). Consistently, FMD values increased significantly across categories of the percentage of sites with CAL ≥ 6 mm (p(trend)=0.01) and the periodontitis case definition (p(trend)=0.006). Restrictions to subjects without antihypertensive or statin medication or current non-smokers confirmed previous results. Systemic inflammation did not seem to mediate the relation. Both PPD and CAL were not consistently associated with NMD. In contrast to previous studies, high levels of periodontal disease were significantly associated with high FMD values. This association was not mediated via systemic inflammation. This study revives the discussion on whether and how periodontitis contributes to endothelial dysfunction.

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Periodontitis induces endothelial dysfunction in mice.

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