Involvement of brain-derived neurotrophic factor in exercise‑induced cardioprotection of post-myocardial infarction rats.

International journal of molecular medicine (2018-09-19)
Bi-Lei Wang, Hong Jin, Xi-Qiong Han, Yang Xia, Nai-Feng Liu
RESUMEN

Exercise induces a number of benefits, including angiogenesis in post‑myocardial infarction (MI); however, the underlying mechanisms have not been fully clarified. Neurotrophic brain‑derived neurotrophic factor (BDNF) serves a protective role in certain adult cardiac diseases through its specific receptor, BDNF/NT‑3 growth factors receptor (TrkB). The present study explored the mechanisms by which exercise improves cardiac function, with a focus on the involvement of the BDNF/TrkB axis. MI rats were assigned to Sham, sedentary, exercise, exercise with K252a (a TrkB inhibitor), and exercise with NG‑nitro‑L‑arginine methyl ester (L‑NAME) groups. The exercise group was subjected to 8 weeks of treadmill running. The results demonstrated that the rats in the exercise group exhibited increased myocardial angiogenesis and improved cardiac function, which was attenuated by K252a. Exercise induced activation of the BDNF/TrkB axis in the ischaemic myocardium and increased serum BDNF levels were abated by exposure to L‑NAME. Improvements in angiogenesis and left ventricular function exhibited a positive association, with changes in serum BDNF. In the in vitro experiments, human umbilical vein endothelial cells were exposed to shear stress (SS) of 12 dyn/cm2 to mimic the effects of exercise training on vascular tissue. An increased tube‑forming capacity, and a nitric oxide (NO)‑dependent prolonged activation of the BDNF/TrkB‑full‑length axis over 12 h, but not the TrkB‑truncated axis, was observed. The SS‑related angiogenic response was attenuated by TrkB inhibition. Overall, these results demonstrate that exercise confers certain aspects of its cardioprotective effects through the activation of the BDNF/TrkB axis in an NO‑dependent manner, a process in which fluid‑induced SS may serve a crucial role.

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Sigma-Aldrich
S-Nitroso-N-acetyl-DL-penicillamine, ≥97%, powder
Sigma-Aldrich
L-Penicillamine, 99%