Limb Blood Flow Restriction Plus Mild Aerobic Exercise Training Protects the Heart Against Isoproterenol-Induced Cardiac Injury in Old Rats: Role of GSK-3β

Cardiovascular Toxicology - Tập 19 - Trang 210-219 - 2018
Vida Naderi-Boldaji1,2, Siyavash Joukar3,2, Ali Noorafshan4, Mohammad-Ali Bahreinipour5
1Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Department of Physiology and Pharmacology, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
2Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
3Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Department of Physiology and Pharmacology, Afzalipour Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran
4Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
5Department of Physical Education, Faculty of Shahid Chamran, Kerman Branch, Technical and Vocational University (YVU), Tehran, Iran

Tóm tắt

The present study was conducted to evaluate the effect of blood flow restriction (BFR) training on cardiac resistance to isoproterenol (ISO) induced heart injury in old rats and examined the hypothesis that BFR training may interfere with age-associated impairment of mitochondria by the inhibitory phosphorylation of GSK-3β at Ser9. Old male Wistar rats were divided into the following six groups: CTL (control), ISO (isoproterenol-treated), Sh + ISO (sham-operated plus ISO), BFR + ISO (blood flow restriction plus ISO), Sh-Ex + ISO (sham-operated subjected to exercise and ISO), and BFR-Ex + ISO (blood flow restriction along with exercise and ISO). 10 weeks of exercise training was considered. Then, cardiac injury was induced and physiological, histological, and biochemical parameters were recorded and assessed. Compared to CTL group, isoproterenol administration significantly reduced the systolic arterial pressure (SAP), left-ventricular systolic pressure (LVSP), and ± dp/dt max (P < 0.05). BFR training improved these parameters in the way that BFR-Ex + ISO group had higher SAP, LVSP and ± dp/dt max (P < 0.05) and lower LVEDP (left-ventricular end diastolic pressure) (P < 0.01) than untrained and Sh-Ex + ISO groups. The pS9-GSK-3β and pS9-GSK-3β/GSK-3β ratio were increased in the BFR-Ex + ISO group compared to CTL, ISO, Sh + ISO, and BFR + ISO groups (P < 0.05). The level of plasma cardiac Troponin-I and the severity of the injuries were significantly reduced in BFR-Ex + ISO group versus other cardiac damaged groups. In conclusion, our findings clearly confirmed the cardio-protective effect of BFR training against ISO-induced myocardial injury. Increased phosphorylated GSK-3β and angiogenesis in this model of exercise justify the resistance of old hearts facing stressful situations.

Tài liệu tham khảo

Arshad, J., Sagar, S., & Terzic, A. (2007). Aging and cardioprotection. Journal of Applied Physiology, 103(6), 2120–2128. Narula, J., Jones, M. K., Deng, X., & Tarnawski, A. S. (2010). Impaired angiogenesis in aging myocardial microvascular endothelial cells is associated with reduced importin alpha and decreased nuclear transport of HIF1 alpha: Mechanistic implications. Journal of Physiology and Pharmacology, 61(2), 133–139. Crompton, M. (2004). Mitochondria and aging: A role for the permeability transition. Aging Cell, 3(1), 3–6. Di Lisa, F., Canton, M., Menabò, R., Kaludercic, N., & Bernardi, P. (2007). Mitochondria and cardioprotection. Heart Failure Reviews, 12(3–4), 249–260. Finkel, T., & Holbrook, N. J. (2000). Oxidants, oxidative stress and the biology of ageing. Nature, 408(6809), 239. Yao, H. B., Shaw, P. C., Wong, C. C., & Wan, D. C. (2002). Expression of glycogen synthase kinase-3 isoforms in mouse tissues and their transcription in the brain. Journal of Chemical Neuroanatomy, 23(4), 291–297. Tong, H., Imahashi, K., Steenbergen, C., & Murphy, E. (2002). Phosphorylation of glycogen synthase kinase-3β during preconditioning through a phosphatidylinositol-3-kinase–dependent pathway is cardioprotective. Circulation Research, 90(4), 377–379. Gross, E. R., Hsu, A. K., & Gross, G. J. (2004). Opioid-induced cardioprotection occurs via glycogen synthase kinase β inhibition during reperfusion in intact rat hearts. Circulation Research, 94(7), 960–966. Miura, T., Tanno, M., Miki, T., & Sato, T. (2006). Ser9 phosphorylation of mitochondrial GSK-3β is a primary mechanism of cardiomyocyte protection by erythropoietin against oxidant-induced apoptosis. American Journal of Physiology-Heart and Circulatory Physiology, 295(5), H2079-H2086. Park, S. S., Zhao, H., Mueller, R. A., & Xu, Z. (2006). Bradykinin prevents reperfusion injury by targeting mitochondrial permeability transition pore through glycogen synthase kinase 3β. Journal of Molecular and Cellular Cardiology, 40(5), 708–716. Omar, M. A., Wang, L., & Clanachan, A. S. (2010). Cardioprotection by GSK-3 inhibition: Role of enhanced glycogen synthesis and attenuation of calcium overload. Cardiovascular Research, 86(3), 478–486. Guertin, D. A., & Sabatini, D. M. (2007). Defining the role of mTOR in cancer. Cancer Cell, 12(1), 9–22. Ascensao, A., Lumini-Oliveira, J., Oliveira, J. P., & Magalhaes, J. (2011). Mitochondria as a target for exercise-induced cardioprotection. Current Drug Targets, 12(6), 860–871. Hausenloy, D. J., Lecour, S., & Yellon, D. M. (2011). Reperfusion injury salvage kinase and survivor activating factor enhancement prosurvival signaling pathways in ischemic postconditioning: Two sides of the same coin. Antioxidants & Redox Signaling, 14(5), 893–907. Heusch, G., Boengler, K., & Schulz, R. (2008). Cardioprotection: Nitric oxide, protein kinases, and mitochondria. Circulation, 118(19), 1915–1919. Léger, B., Cartoni, R., Praz, M., Lamon, S., & Dériaz, O. (2006). Akt signalling through GSK-3β, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy. The Journal of Physiology, 576(3), 923–933. Pearson, S. J., & Hussain, S. R. (2015). A review on the mechanisms of blood-flow restriction resistance training-induced muscle hypertrophy. Sports Medicine, 45(2), 187–200. Bahreinipour, M. A., Joukar, S., Hovanloo, F., Najafipour, H., & Naderi-boldaji, V. (2018). Mild aerobic training with blood flow restriction increases the hypertrophy index and MuSK in both slow and fast muscles of old rats: Role of PGC-1α. Life Sciences, 202, 103–109. Raji-Amirhasani, A., Joukar, S., Naderi-boldaji, V., & Bejeshk, M. A. (2018). Mild exercise along with limb blood-flow restriction modulates the electrocardiogram, angiotensin, and apelin receptors of the heart in aging rats. Iranian Journal of Basic Medical Sciences, 21(6), 558–563. Bahreinipour, M. A., Joukar, S., Hovanloo, F., & Najafipour, h (2017). Long-term low-intensity endurance exercise along with blood-flow restriction improves muscle mass and neuromuscular junction compartments in old rats. Iranian Journal of Medical Sciences, 42(6), 569. Joukar, S., Najafipour, H., Dabiri, S. H., Sheibani, M., & Sharokhi, N. (2014). Cardioprotective effect of mumie (shilajit) on experimentally induced myocardial injury. Cardiovascular Toxicology, 4(3), 214–221. Westenbrink, B. D., Ruifrok, W. P., Voors, A. A., & Schoemaker, R. G. (2010). Vascular endothelial growth factor is crucial for erythropoietin-induced improvement of cardiac function in heart failure. Cardiovascular Research, 87(1), 30–39. Zhu, J., Rebecchi, M. J., Glass, P. S., Brink, P. R., & Liu, L. (2011). Cardioprotection of the aged rat heart by GSK-3β inhibitor is attenuated: Age-related changes in mitochondrial permeability transition pore modulation. American Journal of Physiology-Heart and Circulatory Physiology, 300(3), H922–H930. Noorafshan, A. (2014). Stereology as a valuable tool in the toolbox of testicular research. Annals of Anatomy, 196(1), 57–66. Joukar, S., Sheibani, M., & Joukar, F. (2012). Cardiovascular effect of nifedipine in morphine dependent rats: Hemodynamic, histopathological, and biochemical evidence. Croatian Medical Journal, 53(4), 343–349. Mühlfeld, C., Nyengaard, J. R., & Mayhew, T. M. (2010). A review of state-of-the-art stereology for better quantitative 3D morphology in cardiac research. Cardiovascular Pathology, 19(2), 65–82. Rona, G., Chappel, C. I., Balazs, T., & Gaudry, R. (1959). An infarct-like myocardial lesion and other toxic manifestations produced by isoproterenol in the rat. Archives of Pathology & Laboratory Medicine, 67, 443–455. Duchen, M. R. (2004). Mitochondria in health and disease: Perspectives on a new mitochondrial biology. Molecular Aspects of Medicine, 25(4), 365–451. Aminizadeh, S., Marefati, H., Najafipour, H., Joukar, S., Dabiri, Sh, & Shahouzehi, B. (2016). Protective effects of high-intensity versus low-intensity interval training on isoproterenol-induced cardiac injury in wistar rats. Research in Cardiovascular Medicine, 6(1), 5. Naderi-Boldaji, V., Joukar, S., Noorafshan, A., Raji-amirhasani, A., Naderi-Boldaji, S., & Bejeshk, M. A. (2018). The effect of blood flow restriction along with low-intensity exercise on cardiac structure and function in aging rat: Role of angiogenesis. Life Sciences, 15(209), 202–209. Abe, T., Fujita, S, Nakajima, T., Sakamaki, M., & Ozaki, H. (2010). Effects of low-intensity cycle training with restricted leg blood flow on thigh muscle volume and VO2 max in young men. Journal of Sports Science & Medicine, 9(3), 452–458. Park, S., Kim, J. K., Choi, H. M., Kim, H. G., Beekley, M. D., & Nho, H. (2010). Increase in maximal oxygen uptake following 2-week walk training with blood flow occlusion in athletes. European Journal of Applied Physiology, 109(4), 591–600. Corvino, R. B., Denadai, B. S., Caputo, F., & dos Santos, R. P. (2014). Four weeks of blood flow restricted training increases time to exhaustion at severe intensity cycling exercise. Revista Brasileira de Cineantropometria & Desempenho Humano, 16(5), 557–570. Oliveira, M. F. M., Caputo, F., Corvino, R. B., & Denadai, B. S. (2016). Short-term low-intensity blood flow restricted interval training improves both aerobic fitness and muscle strength. Scandinavian Journal of Medicine & Science in Sports, 26(9), 017–1025. Ascensão, A., Lumini-Oliveira, J., Machado, G., & Ferreira, R. M., & Gonçalves, I. O. (2011). Acute exercise protects against calcium-induced cardiac mitochondrial permeability transition pore in doxorubicin treated rats. Clinical Science, 120(1), 37–49. Wu, Y., Peng, H., Cui, M., Whitney, N. P., Huang, Y., & Zheng, C. J. (2009). CXCL12 increases human neural progenitor cell proliferation through Akt-1/FOXO3a signaling pathway. Journal of Neurochemistry, 109(4), 1157–1167. Pons, S., Martin, V., Portal, L., Zini, R., & Morin, D. (2013). Regular treadmill exercise restores cardioprotective signaling pathways in obese mice independently from improvement in associated co-morbidities. Journal of Molecular and Cellular Cardiology, 54, 82–89. Miura, T., Nishihara, M., & Miki, T. (2009). Drug development targeting the glycogen synthase kinase-3beta (GSK-3beta)-mediated signal transduction pathway: Role of GSK-3beta in myocardial protection against ischemia/reperfusion injury. Pharmacolgical Science, 109(2), 162–167. Lim, S. Y., Davidson, S. M., Hausenloy, D. J., & Yellon, D. M. (2007). Preconditioning and postconditioning: The essential role of the mitochondrial permeability transition pore. Cardiovascular Research, 75(3), 530–535. Miura, T., & Miki, T. (2009). GSK-3β, a therapeutic target for cardiomyocyte protection. Circulation Journal, 73(7), 1184–1192. Izem-Meziane, M., Djerdjouri, B., Rimbaud, S., & Caffin, F. (2011). Catecholamine-induced cardiac mitochondrial dysfunction and mPTP opening: Protective effect of curcumin. American Journal of Physiology-Heart and Circulatory Physiology, 302(3), H665–H674.