Abstract
Purpose
The aim of this study was to investigate whether skeletal muscle-derived follistatin-like 1 (FSTL1) reaches the heart and exerts the angiogenetic function in rats suffering myocardial infarctions (MI) after exercise intervention.
Methods
Forty-eight male adult Sprague–Dawley rats were randomly divided into four groups. MI was provoked by ligation of left anterior descending coronary artery. MI rats underwent adeno-associated virus injection of FST1 in tibialis anterior muscle and 4 weeks of resistance exercise via a tail-suspended incremental weight-climbing method (0–75% body weight, daily load increased by 10%; 1 h/day, 5 day/w). Heart function was evaluated by hemodynamics including LVSP, LVEDP and ± dP/dt max; the cross-sectional area of muscle cells and myocardium fibrosis were analyzed by DiI and Masson’s staining, respectively; the FSTL1 expression, endothelial cell proliferation and angiogenesis were visualized by immunofluorescence staining; and protein expression was quantified by Western blotting.
Results
Resistance exercise reverted MI-induced skeletal muscle atrophy, increased muscle FSTL1 expression and stimulated skeletal muscle derived FSTL1 entering into the MI heart via blood circulation. The overexpression of skeletal muscle FSTL1 improved myocardial endothelial cell proliferation, increased small vessel density in the fibrotic border, inhibited myocardial fibrosis and improved heart function in the MI rats after the exercise intervention. Meanwhile, DIP2A-PI3K-Akt-mTOR, Erk1/2 and TGFβ-Smad2/3 pathways were activated in the myocardium.
Conclusion
Resistance exercise stimulates skeletal muscle derived FSTL1 to reach the myocardium which makes a positive contribution to cardioprotection in MI rat.
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Acknowledgements
This work was supported by National Natural Science Foundation of China (No. 31371199).
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Xi, Y., Hao, M. & Tian, Z. Resistance Exercise Increases the Regulation of Skeletal Muscle FSTL1 Consequently Improving Cardiac Angiogenesis in Rats with Myocardial Infarctions. J. of SCI. IN SPORT AND EXERCISE 1, 78–87 (2019). https://doi.org/10.1007/s42978-019-0009-4
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DOI: https://doi.org/10.1007/s42978-019-0009-4