2023 Fiscal Year Final Research Report

Roles of beta-adrenoceptor signaling in Porphyromonas gingivalis lipopolysaccharide-induced cardiac dysfunction

Research Project

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Project/Area Number	20K10304
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 57080:Social dentistry-related
Research Institution	Tsurumi University
Principal Investigator	Ohnuki Yoshiki 鶴見大学, 歯学部, 講師 (50288114)
Co-Investigator(Kenkyū-buntansha)	梅木大輔鶴見大学, 歯学部, 助教 (10514937) 成山明具美鶴見大学, 歯学部, 助教 (90440304)
Project Period (FY)	2020-04-01 – 2024-03-31
Keywords	歯周病 / 心疾患 / リポ多糖 / β受容体 / Porphyromonas gingivalis / プロプラノロール
Outline of Final Research Achievements	Periodontitis, an oral infection, is known to be a risk factor for cardiovascular diseases. However, the precise mechanisms involved remain elusive. In the present study, we investigated in mice the roles of β-adrenoceptor signaling in cardiac dysfunction induced by the administration of lipopolysaccharide derived from Porphyromonas gingivalis (Pg-LPS) for 1 week at a dose (0.8 mg/kg/day) equivalent to the circulating level in patients with periodontal disease. Cardiac function evaluated with left ventricular ejection fraction was significantly decreased by the Pg-LPS treatment, but the coadministration of propranolol, a non-selective β-blocker, ameliorated the dysfunction. Cardiac fibrosis and myocyte apoptosis were significantly increased by the Pg-LPS treatment, but propranolol blocked these changes. These results suggest that Pg-LPS induces cardiac dysfunction in association with cardiac remodeling via activation of β-adrenoceptor signaling.
Free Research Field	生理学
Academic Significance and Societal Importance of the Research Achievements	口腔疾患と心疾患の関連性は疫学調査から示唆されているが、その因果関係やメカニズムに関する詳細な報告は少ない。本研究では、主要な歯周病原性細菌由来の内毒素の慢性投与により作製した歯周病モデルマウスを用い、口腔機能障害と心疾患の因果関係およびその分子機序を解明した。また、得られた研究成果から、β受容体シグナル経路をターゲットとした治療法が歯周病を伴う心疾患に対して有効であることも示唆された。高齢化社会を迎え、近年増加傾向にある歯周病などの口腔疾患と、死亡原因第2位の心疾患との関連性を調べた本研究の意義はきわめて高い。