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Occlusal disharmony accelerates the initiation of atherosclerosis in apoE knockout rats

Daisuke Ekuni1*, Toshiki Yoneda1, Yasumasa Endo1, Kenta Kasuyama1, Koichiro Irie2, Shinsuke Mizutani1, Tetsuji Azuma1, Takaaki Tomofuji13 and Manabu Morita1

Author Affiliations

1 Department of Preventive Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan

2 Department of Preventive Dentistry and Dental Public Health, Aichi-Gakuin University, Kusumoto-cho, Chikusa-ku, Nagoya 464-8650, Japan

3 Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan

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Lipids in Health and Disease 2014, 13:144  doi:10.1186/1476-511X-13-144

Published: 5 September 2014



Psychosocial stress is one of the risk factors for atherosclerosis. As occlusal disharmony induces psychological stress, we hypothesized that psychological stress by occlusal disharmony accelerates atherosclerosis. The aim of this study was to investigate the effects of occlusal disharmony on the initiation of atherosclerosis in apolipoprotein E (apoE) knockout rats.


Fourteen male apoE-knockout rats (age; 8 weeks) (Sprague–Dawley strain background) were divided into two groups of seven rats: the occlusal disharmony group and the no treatment (control) group. In the occlusal disharmony group, the maxillary molar cusps were cut off for the 8-week experimental period.


In the occlusal disharmony group, the percentages of the area of total aortic lumen occupied by plaques and lipid were significantly higher than those in the control group (p < 0.05, t-test). The occlusal disharmony group also showed significantly higher serum levels of very low-density lipoprotein-cholesterol (VLDL) and low-density lipoprotein-cholesterol (LDL), plasma levels of corticosterone (1.9, 1.3 and 1.3 times, respectively), higher aortic protein expression levels of vascular cell adhesion molecule-1 (VCAM1) and intercellular adhesion molecule-1 (ICAM1) (1.5 and 1.4 times, respectively), and higher aortic gene expression of levels of VCAM1 and Toll-like receptor 4 (TLR4) (1.9 and 4.3 times, respectively), as compared to the control group (p < 0.05). However, there were no significant differences in serum levels of oxidized LDL, reactive oxygen metabolites and C-reactive protein between the two groups.


In apoE knockout rats, occlusal disharmony may induce VCAM1, ICAM1 and TLR4 expression and accelerate the initiation of atherosclerosis.

Apolipoprotein E; Atherosclerosis; Occlusion; Stress; Toll-like receptor; Vascular cell Adhesion molecule-1