Reactive Oxygen Species Cause Exercise-Induced Angina in a Myocardial Ischaemia-Reperfusion Injury Model.

Xiaohang Wang,Koichi Noguchi,Yi Dai,Hirosato Kanda,Satoshi Yamamoto,Taichi Sakaguchi,Yoko Kogure,Feng Zhu,Takeshi Tsujino

doi:10.3390/ijms23052820

Abstract

Percutaneous coronary intervention (PCI) effectively treats obstructive coronary artery syndrome. However, 30–40% 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−/− 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.

Highlights

Percutaneous coronary intervention (PCI) is a nonsurgical revascularisation strategy that has been effective in treating obstructive coronary artery disease (CAD), especially for ST-segment elevation myocardial infarction (STEMI)
Considering that H2O2 contributes to the CAD pathogenesis [25], we examined whether H2O2 is produced in the heart during forced treadmill exercise (FTE)
Deletion of transient receptor potential ankyrin-1 (TRPA1) channel in TRPA1−/− mice did not affect the time (s) and number of immobility compared with that in the WT mice (Figure 5E,F). These results strongly suggest that TRPA1 channels, which are expressed on cardiac sensory neurons, are involved in exercise-induced angina development

Summary

Introduction

Percutaneous coronary intervention (PCI) is a nonsurgical revascularisation strategy that has been effective in treating obstructive coronary artery disease (CAD), especially for ST-segment elevation myocardial infarction (STEMI). An important issue about persistent or recurrent angina post-PCI is whether and how cardiac ischaemia recurs in the coronary artery following PCI treatment. Risk factors responsible for cardiac ischaemia recurrence have been clinically investigated These factors include stent thrombosis and in-stent restenosis, which have incidence rates of

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