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Long-term aerobic exercise protects the heart against ischemia/reperfusion injury via PI3 kinase-dependent and Akt-mediated mechanism.
Apoptosis. 2007 Sep; 12(9):1579-88.A

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-3beta 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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Authors+Show Affiliations

Zhang KR
Department of Physiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Liu HT
No affiliation info available
Zhang HF
No affiliation info available
Zhang QJ
No affiliation info available
Li QX
No affiliation info available
Yu QJ
No affiliation info available
Guo WY
No affiliation info available
Wang HC
No affiliation info available
Gao F
No affiliation info available

MeSH

AndrostadienesAnimalsApoptosisCaspase 3Creatine KinaseHeartHydro-LyasesIn Situ Nick-End LabelingMaleMyocardial InfarctionMyocardial Reperfusion InjuryMyocardiumMyocytes, CardiacPhosphatidylinositol 3-KinasesPhysical Conditioning, AnimalProto-Oncogene Proteins c-aktRatsRats, Sprague-DawleySwimmingWortmannin

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17505785

Citation

Zhang, Kun-Ru, et al. "Long-term Aerobic Exercise Protects the Heart Against Ischemia/reperfusion Injury Via PI3 Kinase-dependent and Akt-mediated Mechanism." Apoptosis : an International Journal On Programmed Cell Death, vol. 12, no. 9, 2007, pp. 1579-88.
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. 2007;12(9):1579-88.
Zhang, K. R., Liu, H. T., Zhang, H. F., Zhang, Q. J., Li, Q. X., Yu, Q. J., Guo, W. Y., Wang, H. C., & Gao, F. (2007). Long-term aerobic exercise protects the heart against ischemia/reperfusion injury via PI3 kinase-dependent and Akt-mediated mechanism. Apoptosis : an International Journal On Programmed Cell Death, 12(9), 1579-88.
Zhang KR, et al. Long-term Aerobic Exercise Protects the Heart Against Ischemia/reperfusion Injury Via PI3 Kinase-dependent and Akt-mediated Mechanism. Apoptosis. 2007;12(9):1579-88. PubMed PMID: 17505785.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-term aerobic exercise protects the heart against ischemia/reperfusion injury via PI3 kinase-dependent and Akt-mediated mechanism. AU - Zhang,Kun-Ru, AU - Liu,Hai-Tao, AU - Zhang,Hai-Feng, AU - Zhang,Quan-Jiang, AU - Li,Qiu-Xia, AU - Yu,Qiu-Jun, AU - Guo,Wen-Yi, AU - Wang,Hai-Chang, AU - Gao,Feng, PY - 2007/5/17/pubmed PY - 2007/10/30/medline PY - 2007/5/17/entrez SP - 1579 EP - 88 JF - Apoptosis : an international journal on programmed cell death JO - Apoptosis VL - 12 IS - 9 N2 - 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-3beta 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. SN - 1360-8185 UR - https://www.unboundmedicine.com/medline/citation/17505785/Long_term_aerobic_exercise_protects_the_heart_against_ischemia/reperfusion_injury_via_PI3_kinase_dependent_and_Akt_mediated_mechanism_ L2 - https://doi.org/10.1007/s10495-007-0090-8 DB - PRIME DP - Unbound Medicine ER -