Cardiovascular disease, especially coronary artery disease, remains a major cause of morbidity and mortality in the world, and ischaemia-reperfusion (IR) insult is the main pathological cause leading to death. Exercise training is associated with a reduced risk of cardiovascular disease and the development of cardioprotection against IR injury. Therefore, the purpose of this study was to investigate the effect of preconditioning with high-intensity interval training (HIIT) on myocardial and plasma levels of Klotho and its related axes as novel mechanisms of exercise-induced cardioprotection against IR injury. Seventy male Wistar rats were randomly divided into five groups of control, HIIT, sham, IR and HIIT group that underwent IR injury (H-IR). The training group performed five sessions of HIIT on the treadmill. The cardiac IR injury was induced by ligation of the left anterior descending coronary artery for 30 min followed by 24 h reperfusion. Infarct size and histopathological assessment of cardiac tissues were determined through Evans Bluetriphenyltetrazolium chloride and haematoxylin-eosin staining, respectively. We investigated lipid peroxidation and markers of cardiac injury, antioxidant enzymes and the plasma levels of Klotho using enzyme-linked immunosorbent assays. Also, myocardial levels of Klotho and TRPC6 expression were determined by western blot assays. The results demonstrated a significant increase in myocardial and plasma levels of Klotho following HIIT and a significant decrease during IR injury. Myocardial TRPC6 channel expression increased following IR. HIIT also prevented a significant reduction of Klotho during IR and consequently reduced the expression of the TRPC6 channel in the H-IR group compared with the IR group. Furthermore, HIIT decreased the infarct size, cardiac injury, lipid peroxidation, lactate dehydrogenase, creatine kinase myocardial band and cardiac troponin-I, and improved total antioxidant capacity and catalase, superoxide dismutase and glutathione peroxidase activities following IR injury. The findings of the present study suggest that HIIT improves cardioprotection against IR injury and reduces cardiac damages through an increase in myocardial and plasma levels of Klotho and its related axes (TRPC6 and antioxidant defence). These findings can help to develop preventive and therapeutic approaches.
K E Y W O R D SAntioxidant defence, cardioprotection, high-intensity interval training, Klotho, TRPC6 channels wileyonlinelibrary.com/journal/eph Experimental Physiology. 2020;105:652-665.