High‐intensity interval training increases myocardial levels of Klotho and protects the heart against ischaemia–reperfusion injury

Abstract

New Findings What is the central question of this study? Can a short‐term of HIIT contribute to the reduction of IR injury by enhancing the levels of Klotho and its related axes, including myocardial TRPC6 expression, and antioxidant defense as novel possible mechanisms to EICP against IR injury? What is the main finding and its importance? The increasing of plasma and myocardial levels of Klotho as a result of preconditioning with HIIT and preventing a significant reduction of Klotho during IR injury can promote cardioprotection and reduce damage by attenuate the myocardial TRPC6 expression and increased antioxidant defense. Present findings may provide a new mechanism in EICP and IR injury, and Provides the knowledge to develop preventive and therapeutic approaches. Abstract Cardiovascular disease, especially coronary artery disease remains a major cause of morbidity and mortality in the world and ischemia‐reperfusion (IR) insult is the main pathologic cause leads to death during these diseases. Exercise training is associated with a reduced risk of cardiovascular disease and cardioprotection development against IR injury. Therefore, the purpose of this study was to investigate the effect of preconditioning with high‐intensity interval training on myocardial and plasma levels of klotho and its related axes as novel mechanisms to exercise‐induced cardioprotection against IR injury. Seventy male Wistar rats were randomly divided into 5 groups of Control, HIIT, Sham, IR, and H‐IR. The training group performed 5 sessions of high intensity interval training on the treadmill. The cardiac IR injury was induced by LAD ligation for 30 min followed by 24 h reperfusion. Infarct size and histopathological assessment of cardiac tissues were determined through Evans Blue‐TTC and H&E staining respectively. We investigated lipid peroxidation and markers of cardiac injury, antioxidant enzymes, and the plasma levels of klotho using the ELISA assay. Also, myocardial levels of Klotho and TRPC6 expression was determined by western blot assay. The results demonstrated a significant increase in myocardial and plasma levels of Klotho following HIIT and a significant decrease during IR injury. The myocardial TRPC6 channels expression increased following IR. The HIIT also prevented a significant reduction of the Klotho during IR and consequently reduced the expression of TRPC6 channel in the H‐IR group compared the IR group. Furthermore, HIIT decreased the infarct size, cardiac injury, lipid peroxidation, LDH, CK‐MB, and cTnI and improved TAC, CAT, SOD, GPx activities and antioxidant system 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 defense). These findings can help to develop preventive and therapeutic approaches. This article is protected by copyright. All rights reserved