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Long-term aerobic exercise protects the heart against ischemia/reperfusion injury via PI3 kinase-dependent and Akt-mediated mechanism

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Abstract

Objective

Physical activity has been shown to improve cardiovascular function and to be beneficial to type 2 diabetic patients. However, the effects of aerobic exercise (AE) on myocardial ischemia/reperfusion (MI/R) are largely unclear. Therefore, the aims of the present study were to determine whether long-term AE can protect the heart against I/R injury, and if so, to investigate the underlying mechanism.

Methods

Adult male Sprague–Dawley rats were randomly subjected to 8 weeks of either sedentary or free-loading swimming exercise (3 h/day, 5 d/week). Then the animals were subjected to 30 min MI followed by 4 h R. Arterial blood pressure and left ventricular pressure (LVP) were monitored throughout the whole MI/R procedure. Plasma creatine kinase (CK) and lactate dehydrogenase (LDH) activities were measured spectrophotometrically. Myocardial infarction and myocardial apoptosis (TUNEL analysis) were determined in a blinded manner.

Results

MI/R caused significant cardiac dysfunction and myocardial apoptosis (strong TUNEL-positive staining). Compared with sedentary group, rats subjected to 8 weeks of AE showed protection against MI/R as evidenced by reduced myocardial infarction (26.8 ± 1.5% vs. 35.3 ± 2.4%, n = 8, P < 0.05), inhibited cardiomyocyte apoptosis (decreased apoptotic index (12.4 ± 1.1% vs. 21.0 ± 1.7%, n = 8, P < 0.01) and decreased myocardial caspase-3 activity), decreased plasma CK and LDH activities and improved recovery of cardiac systolic/diastolic function (including LVSP and ±LVdP/dt) at the end of R. Moreover, exercise resulted in 1.7-fold, 2.5-fold and 2.5-fold increases in Akt expression, Akt phosphorylation and glycogen synthase kinase-3β phosphorylation in I/R myocardium, respectively (n = 3, all P < 0.05). More importantly, treatment with wortmannin, a PI3 kinase inhibitor, 15 min before R not only significantly blocked Akt phosphorylation (P < 0.05) in exercise rats, but also abolished long-term AE-induced cardioprotection for the I/R heart as manifested by increased apoptosis and myocardial infarction, and reduced cardiac function.

Conclusion

Long-term AE exerts cardioprotective effect against MI/R injury, including anti-cardiomyocyte apoptosis, which is at least partly via PI3 kinase-dependent and Akt-mediated mechanism.

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Acknowledgments

This study was supported by National Science Fund for Outstanding Young Investigators (No. 30625033) and grants from the National Natural Science Foundation of China (Nos. 30471923, 30500577).

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Authors and Affiliations

  1. Departments of Physiology and Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China

    Kun-Ru Zhang, Hai-Tao Liu, Hai-Feng Zhang, Quan-Jiang Zhang, Qiu-Xia Li, Qiu-Jun Yu, Wen-Yi Guo, Hai-Chang Wang & Feng Gao

  2. Sport College of Shaanxi Normal University, Xi’an, 710062, China

    Kun-Ru Zhang

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  1. Kun-Ru Zhang
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Correspondence to Feng Gao.

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Zhang, KR., Liu, HT., Zhang, HF. et al. Long-term aerobic exercise protects the heart against ischemia/reperfusion injury via PI3 kinase-dependent and Akt-mediated mechanism. Apoptosis 12, 1579–1588 (2007). https://doi.org/10.1007/s10495-007-0090-8

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  • DOI: https://doi.org/10.1007/s10495-007-0090-8

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