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Exercise Training Stabilizes RyR2-Dependent Ca 2+ Release in Post-infarction Heart Failure
Dysfunction of the cardiac ryanodine receptor (RyR2) is an almost ubiquitous finding in animal models of heart failure (HF) and results in abnormal Ca release in cardiomyocytes that contributes to contractile impairment and arrhythmias. We tested whether exercise training (ET), as recommended by cur...
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Published in: | Frontiers in cardiovascular medicine 2020, Vol.7, p.623922 |
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Main Authors: | , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Online Access: | Get full text |
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Summary: | Dysfunction of the cardiac ryanodine receptor (RyR2) is an almost ubiquitous finding in animal models of heart failure (HF) and results in abnormal Ca
release in cardiomyocytes that contributes to contractile impairment and arrhythmias. We tested whether exercise training (ET), as recommended by current guidelines, had the potential to stabilize RyR2-dependent Ca
release in rats with post-myocardial infarction HF.
We subjected male Wistar rats to left coronary artery ligation or sham operations. After 1 week, animals were characterized by echocardiography and randomized to high-intensity interval ET on treadmills or to sedentary behavior (SED). Running speed was adjusted based on a weekly VO
test. We repeated echocardiography after 5 weeks of ET and harvested left ventricular cardiomyocytes for analysis of RyR2-dependent systolic and spontaneous Ca
release. Phosphoproteins were analyzed by Western blotting, and beta-adrenoceptor density was quantified by radioligand binding.
ET increased VO
in HF-ET rats to 127% of HF-SED (
< 0.05). This coincided with attenuated spontaneous SR Ca
release in left ventricular cardiomyocytes from HF-ET but also reduced Ca
transient amplitude and slowed Ca
reuptake during adrenoceptor activation. However, ventricular diameter and fractional shortening were unaffected by ET. Analysis of Ca
homeostasis and major proteins involved in the regulation of SR Ca
release and reuptake could not explain the attenuated spontaneous SR Ca
release or reduced Ca
transient amplitude. Importantly, measurements of beta-adrenoceptors showed a normalization of beta
-adrenoceptor density and beta
:beta
-adrenoceptor ratio in HF-ET.
ET increased aerobic capacity in post-myocardial infarction HF rats and stabilized RyR2-dependent Ca
release. Our data show that these effects of ET can be gained without major alterations in SR Ca
regulatory proteins and indicate that future studies should include upstream parts of the sympathetic signaling pathway. |
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ISSN: | 2297-055X 2297-055X |