Mechanism of cardiac disease induced by periodontal disease and its therapeutic target of Epac1

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K06862
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Tsurumi University
• Principal Investigator: Okumura Satoshi 鶴見大学, 歯学部, 教授 (60233475)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 歯周病 / アポトーシス / 線維化 / 細胞内伝達

Outline of Final Research Achievements

Lipopolysaccharide (LPS) is well known to activate Toll-like receptor 4 (TLR4) signaling and induce cardiac dysfunctions. The aim of the present study was to investigate the effects of LPS derived from Porphylomonas gingivalis (PG-LPS) on cardiac function in mice with or without an inhibitor of TLR4 signaling (TAK-242) for 4 weeks. Mice were divided into 4 groups:1) Control 2) PG-LPS-treated group, 3) TAK-242-treated group, and 4) PG LPS+TAK-treated groups. We first examined cardiac function by echocardiography and found that cardiac function was significantly decreased by the treatment of PG-LPS, but TAK-242 protected the dysfunction. Cardiac fibrosis (Masson-trichrome staining) and myocyte apoptosis (TUNEL staining) were significantly increased by the treatment of PG-LPS, but TAK-242 blocked these changes. These data suggest that chronic PG-LPS infusion might play an important role for the development of cardiac dysfunction via activation of TLR4 signaling.

Free Research Field

生理学

Academic Significance and Societal Importance of the Research Achievements

歯周病と心疾患の関連性については、疫学的に関連があるという報告は多いが、一方で最近米国心臓病協会(AHA)より、因果関係について断定できる確証はないことが報告された (Lockhart PB et al. Circulation 2021)。本研究より歯周病の罹患を予防することは、健康寿命の延伸に重要であることが理解されれば、欧米諸国に比較して低い我国の歯科検診受診率は向上し(スウェーデン90%,アメリカ 80%,イギリス 70%, 日本6%)、日本歯科医師会と厚生労働省が推進する8020運動(80歳以上でも自分の歯を20本以上保つことで豊かな人生を)の達成率増加にも貢献すると期待される。