{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:58:01Z","timestamp":1788357481754,"version":"build-2803163510"},"reference-count":58,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hyogo Innovative Challenge Grant of Hyogo College of Medicine and the Chinese Medicine Confucius Institute at Hyogo College of Medicine Research Grants.","award":["DY"],"award-info":[{"award-number":["DY"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Percutaneous coronary intervention (PCI) effectively treats obstructive coronary artery syndrome. However, 30\u201340% patients continue to have angina after a successful PCI, thereby reducing patient satisfaction. The mechanisms underlying persistent angina after revascularisation therapy are still poorly understood; hence, the treatment or guideline for post-PCI angina remains unestablished. Thus, this study aimed to investigate the mechanisms underlying effort angina in animals following myocardial ischaemia-reperfusion (I\/R) injury. Phosphorylated extracellular signal-regulated kinase (p-ERK), a marker for painful stimulation-induced neuronal activation, was used for the investigation. After a forced treadmill exercise (FTE), the number of p-ERK-expressing neurons increased in the superficial dorsal horn of the I\/R model animals. Moreover, FTE evoked hydrogen peroxide (H2O2) production in the I\/R-injured heart, inducing angina through TRPA1 activation on cardiac sensory fibres. Notably, the treatment of a TEMPOL, a reactive oxygen species scavenger, or TRPA1\u2212\/\u2212 mice successfully alleviated the FTE-induced p-ERK expression in the dorsal horn. The production of H2O2, a reactive oxygen species, through physical exercise contributes to angina development following I\/R. Hence, our findings may be useful for understanding and treating angina following revascularisation therapy.<\/jats:p>","DOI":"10.3390\/ijms23052820","type":"journal-article","created":{"date-parts":[[2022,3,6]],"date-time":"2022-03-06T20:38:16Z","timestamp":1646599096000},"page":"2820","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Reactive Oxygen Species Cause Exercise-Induced Angina in a Myocardial Ischaemia-Reperfusion Injury Model"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0949-2673","authenticated-orcid":false,"given":"Xiaohang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Surgery, Hyogo College of Medicine, Nishinomiya 663-8501, Hyogo, Japan"},{"name":"Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe 650-8530, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2547-9073","authenticated-orcid":false,"given":"Hirosato","family":"Kanda","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe 650-8530, Hyogo, Japan"},{"name":"Department of Anatomy and Neuroscience, Hyogo College of Medicine, Nishinomiya 663-8501, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Tsujino","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe 650-8530, Hyogo, Japan"},{"name":"Department of Cardiovascular and Renal Medicine, Hyogo College of Medicine, Nishinomiya 663-8501, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoko","family":"Kogure","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe 650-8530, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe 650-8530, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6408-626X","authenticated-orcid":false,"given":"Satoshi","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe 650-8530, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taichi","family":"Sakaguchi","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery, Hyogo College of Medicine, Nishinomiya 663-8501, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Noguchi","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neuroscience, Hyogo College of Medicine, Nishinomiya 663-8501, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1349-9886","authenticated-orcid":false,"given":"Yi","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Pharmacy, Hyogo University of Health Sciences, Kobe 650-8530, Hyogo, Japan"},{"name":"Department of Anatomy and Neuroscience, Hyogo College of Medicine, Nishinomiya 663-8501, Hyogo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2455","DOI":"10.1093\/eurheartj\/ehy857","article-title":"Mechanisms and diagnostic evaluation of persistent or recurrent angina following percutaneous coronary revascularization","volume":"40","author":"Crea","year":"2019","journal-title":"Eur. 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