Investigation of key molecules for exercise-induced bradycardia: involvement of oxidative stress in functional regulation of the cardiac pacemaker

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K15017
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 48020:Physiology-related
• Research Institution: Ritsumeikan University
• Principal Investigator: NAKAO Shu 立命館大学, 生命科学部, 助教 (30646956)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: 心臓 / 不整脈 / 心臓刺激伝導系 / 分子生物学 / 生理学 / 酸化ストレス / 運動 / 代謝

Outline of Final Research Achievements

We have investigated the underlying mechanisms of exercise-induced bradyarrhythmias using exercise mouse model, but signaling molecules involved in these arrhythmias remain unknown. In this study, we hypothesized whether exercise-induced oxidative stress causes pacemaker dysfunction. Transcriptome analysis from sedentary and trained mouse sinoatrial node, primary pacemaking site, revealed over 4,000 genes were downregulated by exercise, and cardiac pacemaking genes were also affected, whereas the expression pattern of genes related to oxidative stress were not significantly changed. Moreover, anti-oxidant agent resveratrol treatment slightly improved exercise-induced slowed heart rate.

Free Research Field

心臓生理学

Academic Significance and Societal Importance of the Research Achievements

有酸素運動によって過剰に増加する酸化ストレスが運動誘発性不整脈に関与していることを示唆する傍証は得られていないが、遺伝子発現の網羅的解析によって予想外の遺伝子群の変動が認められた。今後、従来より関連付けられている「運動と酸化ストレス」だけでなく、本研究から得られた新たな視点からメカニズム解明を目指すことで、不整脈全般に関わる新規病態因子の発見につながっていくことを期待する。