Abstract

Tooth loss or incorrect positioning causes occlusal disharmony. Furthermore, tooth loss and atrial fibrillation (AF) are both risk factors for ischemic stroke and coronary heart disease. Therefore, we hypothesized that occlusal disharmony-induced stress increases susceptibility to AF, and we designed the present study to test this idea in mice. Bite-opening (BO) was done by cementing a suitable appliance onto the mandibular incisor to cause occlusal disharmony by increasing the vertical height of occlusion by 0.7 mm for a period of 2 weeks. AF susceptibility, evaluated in terms of the duration of AF induced by transesophageal burst pacing, was significantly increased concomitantly with atrial remodeling, including fibrosis, myocyte apoptosis and oxidative DNA damage, in BO mice. The BO-induced atrial remodeling was associated with increased calmodulin kinase II-mediated ryanodine receptor 2 phosphorylation on serine 2814, as well as inhibition of Akt phosphorylation. However, co-treatment with propranolol, a non-selective β-blocker, ameliorated these changes in BO mice. These data suggest that improvement of occlusal disharmony by means of orthodontic treatment might be helpful in the treatment or prevention of AF.

Highlights

  • Bax Bcl-2-associated protein Bcl-2 B cell lymphoma-2 protein polyvinylidene fluoride (PVDF) Polyvinylidene fluoride Tris-buffered saline-0.05% (v/v) Tween20 (TBS-T) Tris-buffered saline-0.05% (v/v) Tween[20] GAPDH Glyceraldehyde-3-dehydrogenase

  • adenylyl cyclase (AC) in turn converts adenosine triphosphate (ATP) into cyclic adenosine monophosphate, which facilitates downstream signaling via protein kinase A/exchange protein activated by the cAMP (Epac) signaling ­pathway[19,20,21,22]

  • This link may be explained by chronic inflammation and repeated bacteremia from the oral cavity via periodontal disease, as inflammation plays an important role in the pathogenesis of a­ therosclerosis[44]

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Summary

Introduction

Bax Bcl-2-associated protein Bcl-2 B cell lymphoma-2 protein PVDF Polyvinylidene fluoride TBS-T Tris-buffered saline-0.05% (v/v) Tween[20] GAPDH Glyceraldehyde-3-dehydrogenase. Extensive studies have shown that periodontal disease is associated with elevations of several markers of chronic inflammation, and it might be a factor in the etiology of cardiovascular ­disease[7,8,9,10,11]. Men with 0–10 teeth was demonstrated to be a significantly higher risk of cardiovascular disease than men with 25–32 teeth, independent of the history of periodontal d­ isease[12], suggesting that other factors, such as occlusal disharmony, might contribute to the association between oral health and cardiovascular disease. Occlusal disharmony has been shown to elevate the plasma level of corticosteroid, a marker of chronic stress, resulting in stimulation of the hypothalamus–pituitary–adrenal a­ xis[13]. The effects of occlusal disharmony on the downstream ß-AR/Gsα/cAMP signaling remain poorly understood

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