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

Int Endod J. 2020 Jun;53(6):812-823. doi: 10.1111/iej.13279. Epub 2020 Mar 9.


Aim: First, 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.

Methodology: Using 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.

Results: Both 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.

Conclusions: A 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.

Keywords: apical periodontitis; atherosclerosis; inflammation.

MeSH terms

  • Animals
  • Atherosclerosis*
  • Cytokines
  • Disease Models, Animal
  • Inflammation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Periapical Periodontitis*


  • Cytokines