Apical Periodontitis as a Contributive Risk Factor for Atherosclerosis

• Author / Creator

  Berlin-Broner, Yuli

• Background and Objectives: Atherosclerosis is a chronic inflammatory process which leads to heart disease and death. Apical periodontists (AP) is a common inflammatory condition associated with infected teeth. In a recent systematic review, we identified a positive association between AP and cardiovascular disease; however, no studies examined causality. The overall goal of our study was to determine if there is evidence for a causal relationship between AP and atherosclerosis. To investigate mechanisms and causality, we created a mouse model to determine whether AP increases the risk for atherosclerosis. Our specific aims were to determine whether there is a difference between mice with AP and mice without AP in (1) Atherosclerosis lesion burden (percentage of atherosclerotic lesion area compared to the total aortic area). (2) Levels of systemic inflammation (inflammatory cytokines in the plasma). (3) Levels of systemic oxidative stress, as measured by the levels of nitrotyrosine. Hypothesis: We hypothesize that mice with AP, as compared to mice without AP, will show increased atherosclerosis lesion burden, increased levels of systemic inflammation and nitrotyrosine. Methods: AP was induced in the pro-atherogenic low-density lipoprotein receptor knockout (LDLR KO) mouse model by exposing the dental pulp of four molars in each mouse in the AP group (Rx) (n=17). Controls received only anesthesia (n=23). Mice were fed a high-fat, Western diet to induce atherosclerosis. Plasma was collected to characterize the inflammatory profile (cytokine array) at eight and 16 weeks after AP induction. At 16 weeks, the mice were euthanized and the aortas were collected to measure the atherosclerosis lesion burden (oil red O staining). AP lesions were validated using micro-CT and histology. Results: There were no differences in weight gain or levels of total plasma cholesterol between the groups at 16 weeks. These data show that these risk factors of atherosclerosis will not potentially confound our results. Despite our hypothesis that mice in the Rx group would show an increase in atherosclerosis lesion burden as compared to the sham group, we found they, in fact, developed a similar degree of atherosclerosis (lesion area in the Rx group 7.65 ± 0.47%, compared with 7.46 ± 0.44% in the sham group, p=0.77). The similar atherosclerosis lesion burden percentages in both groups are aligned with the lack of difference in pro-atherogenic cytokines. Lack of difference in both of the above can be explained by the variability in the number of periapical lesions within the Rx group, which might have resulted in local inflammation below the level of creating a systemic inflammatory difference. Significance: To our best knowledge, this is the first study using the LDLR KO mouse model for atherosclerosis to study the influence of AP. Although no difference was found between the groups, we recommend viewing this study as a launch pad for future studies, after addressing the challenges which are discussed in the manuscript. Since AP still has the potential to have a contributive role in the development of atherosclerosis, this area should be further explored.

• Subjects / Keywords

  • atherosclerosis
  • apical periodontitis

• Graduation date

  Fall 2018

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R38G8G02Z

• License

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