Analysis of the pathogenesis of atrial fibrillation induced by oral disease via a cAMP target molecule Epac
| Project/Area Number |
20K10305
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 57080:Social dentistry-related
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| Research Institution | Tsurumi University |
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Principal Investigator |
Suita Kenji 鶴見大学, 歯学部, 助教 (90569542)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 口腔疾患 / 心房細動 / cAMP / Epac / βアドレナリン受容体シグナル / 心臓組織リモデリング / 心臓リモデリング / ストレス / 自律神経系 / 心機能 / 口腔機能異常 / ベータアドレナリン受容体 |
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| Outline of Research at the Start |
口腔疾患と心疾患の連関を示唆する研究報告は数多いが、その分子機構の詳細は依然として明らかでない。これまでに研究代表者は、心臓βアドレナリン受容体（β-AR）シグナルの構成因子であるEpac1に着目し、臨床で最も一般的な不整脈である心房細動（AF）の発症における当該分子の役割を報告した。本研究では、我々が最近構築した口腔疾患の動物モデルを用い、AF発症における口腔疾患の影響をEpac1遺伝子欠損（Epac1KO）マウスと野生型マウスで比較検討する。すなわち、口腔疾患がAFのリスクファクターであることを明らかにし、その発症機構におけるEpac1を介したβ-ARシグナル伝達経路の重要性を証明する。
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| Outline of Final Research Achievements |
The aim of this study was to clarify the relationship between oral diseases and atrial fibrillation (AF), one of the most prevalent arrhythmias, using mouse model of oral disease. Occlusal disharmony, which is caused by increasing the vertical height of occlusion by 0.7 mm for 2 weeks, induced the remodeling of atrial tissue, and increased the susceptibility to AF by chronic activation of sympathetic nervous system. In acute phase after occlusal disharmony induction, there was a significant decrease of cardiac function and an increase of early mortality in Epac (exchanged protein directly activated by cAMP)1-knockout mice as compared to wild-type mice. This result suggested that occlusal disharmony may affect the cardiac homeostasis via Epac1-mediated signaling.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、AFのリスクファクターとして知られる高血圧、糖尿病、肥満、睡眠障害などの症状を緩和することがAF治療戦略の重要な柱の１つと考えらえている（Circulation 136, 583-596, 2017）。本研究によりAF予防法ならびに治療法としての口腔保健の重要性がさらに明確になり、国民健康寿命の延伸を目的とした歯科検診や診療の推進運動に貢献できるものと期待される。
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Vidarabine, an anti-herpes agent, prevents occlusal-disharmony-induced cardiac dysfunction in mice2022
Author(s)
Hayakawa Y, Suita K, Ohnuki Y, Mototani Y, Ishikawa M, Ito A, Nariyama M, Morii A, Kiyomoto K, Tsunoda M, Matsuo I, Kawahara H, Okumura S
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Journal Title
J Physiol Sci
Volume: 72
Issue: 1
Pages: 2-16
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effects of chronic Porphylomonas gingivalis lipopolysaccharide infusion on cardiac dysfunction in mice2021
Author(s)
Matsuo I, Ohnuki Y, Suita K, Ishikawa M, Mototani Y, Ito A, Hayakawa Y, Nariyama M, Morii A, Kiyomoto K, Tsunoda M, Gomi K, Okumura S
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Journal Title
J Oral Biosci
Volume: 63
Issue: 4
Pages: 397-400
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effects of occlusal disharmony on susceptibility to atrial fibrillation in mice2020
Author(s)
Suita K, Yagisawa Y, Ohnuki Y, Umeki D, Nariyama M, Ito A, Hayakawa Y, Matsuo I, Mototani Y, Saeki Y, Okumura S
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Journal Title
Sci Rep
Volume: 10(1)
Issue: 1
Pages: 13765-13765
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effects of occlusal disharmony on cardiac fibrosis, myocyte apoptosis and myocyte oxidative DNA damage in mice.2020
Author(s)
Yagisawa Y, Suita K, Ohnuki Y, Ishikawa M, Mototani Y, Ito A, Matsuo I, Hayakawa Y, Nariyama M, Umeki D, Saeki Y, Amitani Y, Nakamura Y, Tomonari H, Okumura
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Journal Title
PLoS One
Volume: 15(7)
Issue: 7
Pages: e0236547-e0236547
DOI
Related Report
Peer Reviewed / Open Access
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