Characterization of a mouse model to study the relationship between apical periodontitis and atherosclerosis

Abstract

AimFirst, to determine the feasibility of using the low‐density lipoprotein receptor knockout (LDLR KO) mouse model to study apical periodontitis (AP). Secondly, to investigate the causal relationship between AP and atherosclerosis. It was hypothesized that it would be feasible to induce AP and atherosclerosis in LDLR KO mice and find a difference in atherosclerosis between AP and Sham groups.MethodologyUsing a published methodology, AP was induced in LDLR KO mice by exposing the dental pulp of the four first molars (Tx). Shams received only anaesthesia. Mice were fed a high fat, Western‐type diet (WTD), to induce atherosclerosis. At 16 weeks, mice were euthanized and aortas collected to measure atherosclerosis lesion burden (oil red O staining). Periapical lesions were validated using micro‐CT and histology. Systemic inflammation was measured using a cytokine array.ResultsBoth groups developed a similar degree of atherosclerosis (mean lesion area 7.46 ± 0.44% in the Tx group compared with 7.65 ± 0.46%, in the Sham group, P = 0.77), and a similar degree of inflammation. Periapical lesions (PALs) in all four molars were only identified in a small subset of Tx mice.ConclusionsA novel mouse model, which combines AP and CVD, was created. This model allows investigation of the relationship between the two diseases, whilst avoiding other potential common confounders. Although no difference in the degree of atherosclerosis was found between the groups, more studies in which the number of periapical lesions, changes in systemic inflammation and the degree of atherosclerosis are correlated are necessary to ultimately determine the impact of AP on CVD.

Cardiac, biochemical and histopathological analysis reveals impaired heart function in hypertensive rats with apical periodontitis

“…There have been no studies that investigated the effect of AP on coronary flow in hypertensive conditions. One of the newest animal studies (Berlin‐Broner et al, 2020) combined AP and atherosclerosis in order to determine the link between this oral disease and changes in the vessel reactivity caused by atherosclerosis. Unlike the present research, the AP was inducted in four molars but without changes in the size of lesions area between the groups.…”

PRIASE 2021 guidelines for reporting animal studies in Endodontology: explanation and elaboration

“…From Berlin‐Broner et al . (2020) – ‘This study was supported by the Canada Foundation for Innovation; Alpha Omega Foundation of Canada Research; University of Alberta, Faculty of Medicine and Dentistry Motyl Graduate Studentship in Cardiac Sciences and Department of Dentistry Fund for Dentistry. We also acknowledge the use of the Department of Dentistry MicroCT, Members of Daniel Graf Lab.…”

“…From Berlin‐Broner et al . (2020) – ‘The number of mice in each group was based on a power calculation from a previous periodontal disease study. In that study, to achieve a P value < 0.05 with 90% power, the sample size was 11 mice per group.…”

“…From Berlin‐Broner et al . (2020) – ‘The authors have stated explicitly that there are no conflicts of interest in connection with this article’.…”

“…From Berlin‐Broner et al . (2020) – ‘Three‐dimensional (3D) micro‐CT scans of mouse heads were taken at 25 μm, 360°, 75 MSec, 50 kV and 0.24 mA (Milabs U‐CT, Utrecht, Netherlands). Scans were reconstructed in MiLabs Software and analysed with Amira software (Thermo Fisher Scientific, Ottawa, ON, Canada).…”