Abstract
Regulated necrosis (necroptosis) plays a pivotal role in the extent of cardiomyocyte loss and the development of post-ischemic adverse remodelling and cardiac dysfunction following myocardial I/R injury. Although HIIT has been reported to give rise to cardioprotection against MI, but the detailed knowledge of its molecular targets for treatment of MI is still not available. The LAD of Male Wistar rats was occluded to induce MI for 30 min and reperfusion for eight weeks. We investigated the effect of long-term HIIT for eight weeks on lipid peroxidation, SOD activity and GSH content using ELISA assay. Cardiac function, fibrosis, and infarct size were assessed by echocardiography, Masson’s trichrome and Evans Blue/TTC dual staining respectively. The expressions of gene markers of myocardial hypertrophy, fibrosis and key mediators of necroptosis were measured using RT-PCR and western blotting assay respectively. The results indicated that HIIT reduced lipid peroxidation, infarct size and improved endogenous antioxidant system and heart function. Significant decreases in mRNA levels of procollagen α1(I), α1(III), and fibronectin1were observed following HIIT. Moreover, that HIIT significantly decreased the expression of key mediators of necroptosis induced by MI (P < 0.05). There were no significant differences in β-MHC mRNA level in different groups. The findings of study suggest that HIIT might exert cardioprotective effects against post-ischemic adverse remodeling through targeting necroptosis process. Likewise, cardioprotective effects of HIIT in coping with myocardial I/R injury may be associated with RIP1-RIP3-MLKL axis. These findings establish a critical foundation for higher efficiency of exercise-based cardiac rehabilitation post–MI and future research.
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Abbreviations
- MI:
-
Myocardial infarction
- I/R:
-
Ischemia/reperfusion
- ROS:
-
Reactive oxygen species
- RIP1:
-
Receptor-interacting protein kinase1
- NF-κB:
-
Nuclear factor-κB
- MLKL:
-
The mixed lineage kinase domain-like protein
- TRPM7:
-
Transient receptor potential melastatin related 7
- HIIT:
-
High-intensity interval training
- MICT:
-
Moderate intensity continuous training
- CExT:
-
Customary continuous exercise training
- LVIDd:
-
Left ventricular diameter in diastole
- LVIDs:
-
Left ventricular diameter in systole
- FS:
-
Fractional shortening
- EF:
-
Ejection fraction
- TBARS:
-
The thiobarbituric acid reactive substance
- TTC:
-
2,3,5- triphenyl-2H-tetrazolium chloride
- MDA:
-
Malondialdehyde
- LAD:
-
Left anterior descending coronary artery
- KCl:
-
Potassium chloride
- NBT:
-
Nitroblue tetrazolium
- GSH:
-
Reduced glutathione
- UCPs:
-
Uncoupling proteins
- eNOS:
-
Endothelial nitric oxide synthase
- CaMKII:
-
Ca2 + _calmodulin–dependent protein kinase
- LDH:
-
Lactate dehydrogenase
- CK:
-
Creatine kinase
- CMT:
-
Continuous Moderately Training
- SOD:
-
Superoxide dismutase
- GAPDH:
-
Glyceraldehyde-3-phosphate Dehydrogenase
- β-MHC:
-
Beta-myosin heavy chain
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Present work was funded by a research grant from Physiology Research Center in Iran University of Medical Science.
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Ghardashi Afousi, A., Gaeini, A., Rakhshan, K. et al. Targeting necroptotic cell death pathway by high-intensity interval training (HIIT) decreases development of post-ischemic adverse remodelling after myocardial ischemia / reperfusion injury. J. Cell Commun. Signal. 13, 255–267 (2019). https://doi.org/10.1007/s12079-018-0481-3
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DOI: https://doi.org/10.1007/s12079-018-0481-3