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Promotion of aging heart function and its redox balance following hind-limb blood flow restriction plus endurance exercise training in rats: klotho and PGC1-α as involving candidate molecules

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Abstract 

Mild to moderate-intensity endurance exercise training combined with hind-limb blood flow restriction (BFR) induces elderly heart rejuvenation and improves cardiac inotropy and resistance to ischemia. However, the mediators of these beneficial effects are still not well known. The present study investigated the possible role of some important molecules in the mediatory of this model of exercise training in the promotion of heart health in aged rats. Male old Wistar rats randomly were divided into control-sham (CTL), hind limbs blood flow restriction (BFR), sham-operated plus 10 weeks’ treadmill exercise training (Ex), and BFR plus exercise (BFR + Ex) groups. Left ventricular end-diastolic pressure (LVEDP), contractility, and Tau indices were measured. ELISA and western blot tests were used for measuring determined cardiac biochemical factors. BFR + Ex displayed significantly lower LVEDP (P < 0.05 and P < 0.01 vs. Ex, and other groups, respectively), improved heart cardiac contractility (P < 0.01), and significantly reduced Tau index in comparison with other groups. BFR + Ex significantly reduced both BAX and BAX to BCL2 ratio (P < 0.05) and as well MDA to TAC ratio (P < 0.05, compared to the CTL group). Also, BFR + Ex significantly increased the level of klotho (P < 0.05) and PGC1-α (P < 0.001) proteins compared to the CTL group but had no significant effect on P-STAT3 expression. Exercise training alone increased Apelin protein (P < 0.05). Our findings suggest that mild to moderate BFR endurance training improves heart performance in the aging rat partly through ameliorating apoptosis, recovering redox balance, improving the longevity factor klotho, and increasing the key energy metabolism regulator PGC1-α.

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Acknowledgements

The data presented in this article are from a PhD thesis (Naser Mahdavi) performed in the Department of Physiology of School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.

Funding

This work was supported by a grant from Kerman University of Medical Sciences, Kerman, Iran, and provided from the results of the PhD Thesis of Mr. N. M.

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Authors and Affiliations

  1. Cardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences and Department of Physiology and Pharmacology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

    Naser Mahdavi & Siyavash Joukar

  2. Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, and Department of Physiology and Pharmacology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

    Siyavash Joukar, Hamid Najafipour & Vida Naderi-boldaji

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  1. Naser Mahdavi
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  2. Siyavash Joukar
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Contributions

S. J. devised the main conceptual ideas and designed the study with N. M., H. N., and V. N. N. M. and V. N. performed the experiments with the supervision of S. J., and H. N. and S. J. supervised all parts of the study and edited the article with input from N. M.

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Correspondence to Siyavash Joukar.

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This animal study was conducted accordance to National Research Council’s Guide for the Care and Use of Laboratory Animals and approved in ethics committee (permission no. IR.KMU.REC.1397.406) of Kerman university of medical science, Kerman, Iran.

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Mahdavi, N., Joukar, S., Najafipour, H. et al. Promotion of aging heart function and its redox balance following hind-limb blood flow restriction plus endurance exercise training in rats: klotho and PGC1-α as involving candidate molecules. Pflugers Arch - Eur J Physiol 474, 699–708 (2022). https://doi.org/10.1007/s00424-022-02702-x

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