1. Introduction
Despite improvements in medical therapy and standard care, exercise-based rehabilitation programs have been shown to have beneficial cardiovascular effects in patients with Myocardial Infarction (MI). Many studies have shown that High-Intensity Interval Training (HIIT) has more protective effects on myocardial tissue than aerobic exercise. Although HIIT has been reported to protect the heart against MI, but accurate knowledge of molecular targets for the treatment of MI is not available yet. Therefore, this study aims to review the current rehabilitation strategies with a special focus on the mechanisms and clinical effects of HIIT in patients with MI.
2. Materials & Methods 
This is a systematic review study. A search was conducted in reputable databases such as PubMed, Science Direct, Google Scholar, Scopus, and Springer on related studies without restriction of publication year using the keywords “microRNAs (miRNA) and myocardial infarction”, “cardiac rehabilitation and myocardial infarction”, “cardiac rehabilitation and High-Intensity Interval Training (HIIT)”, and “High-Intensity Interval Training (HIIT) and myocardial infarction”. The research articles published in reputable journals in English without gender limitations, those included participants diagnosed with MI and those with full details of the training protocol (repetition, intensity and duration), training method, and total duration of the intervention were included in the study. Short papers, lectures or conference papers, unpublished papers, retrospective studies, the studies where participants had heart failure (ejection fraction <40), arrhythmia, or a specific disease (e.g., diabetes, chronic obstructive pulmonary disease, or stroke) were excluded.
3. Results 
According to the studies, HIIT is a safe and effective method to improve cardiac function in patients with MI, and the protective effects of HIIT on coping with myocardial ischemia/reperfusion injury may be related to the RIP1-RIP3-MLKL axis [53]. Studies also showed that low-volume HIIT may be a powerful and effective training to improve functional capacity [56]. In the meantime, low-intensity interval training is more effective in reducing cardiac tissue damage as well as creatinine kinase amount by creating adaptation in increasing inhibitory factors and reducing stimulants in the process of necrosis and apoptosis. Studies showed that HIIT can improve coronary artery circulation, increase mitochondrial muscle function, repair vascular endothelial cells, reduce fibrosis, increase muscle cross-section, and increase physical function. In addition, HIIT can increase plasma and myocardial Klotho protein levels by reducing myocardial TRPC6 expression, enhancing antioxidant defense and the protective effect on the myocardium, and reducing myocardial ischemia reperfusion. Thus, the HIIT exerts significant changes in molecular targets and cell pathway by preventing abnormal changes in mass, size, geometry, and function of heart after MI.
4. Discussion & Conclusion
Receptor-interacting protein 1 (RIP1)-dependent necrosis contributes to long-term cardiac regeneration and post-MI side effects. Necrostatin-1, a specific inhibitor of necroptosis, has been shown to disrupt the interaction between RIP1 and RIP3 to reduce this programmed cell death, inflammatory response, reactive oxygen species production, and subsequent adverse cardiac regeneration [55]. Thus, HIIT can protect against long-term cardiac regeneration after MI by targeting RIP1-dependent necroptosis [50]. These findings confirm the protective effects of long-term HIIT on MI-induced cardiac regeneration and provide a fundamental basis for the higher efficiency of exercise-based cardiac rehabilitation after MI and future research [50]. A low-volume HIIT program (<10 minutes of high-intensity exercise per session) two days a week seems to be an effective stimulus for achieving a clinically improved cardiorespiratory fitness in individuals after MI [15]. Moreover, it was shown that low-volume HIIT multiplies the PGC-1α gene mRNA, which regulates mitochondrial biogenesis in muscle [61]. 
Exercise-induced oxidative stress may increase RNA polymerase III, which plays a key role in the expression of miR-1 and miR-133 genes, thereby reducing cardiac cell apoptosis [61]. Activation of hypoxia-inducible factor-1 alpha (HIF-1 α) or PGC-1α may promote adaptations such as erythropoietin gene expression and endothelial growth factor gene expression, initiating glycolytic enzyme gene expression and reducing the adverse effects of exposure to hypoxia. Activation of HIF-1α along with HIIT reduces oxygen delivery to skeletal muscle; this reduction, like exercise-induced feedback, causes adaptations in blood vessels, including increased RNA polymerase III and increased expression of miR-133 and miR-1 genes [23, 24]. Therefore, HIIT targets myocardial necroptosis caused by oxidative stress and protects the heart against adverse left ventricular regeneration after MI. It can be considered in post-MI cardiac rehabilitation programs.

Ethical Considerations
Compliance with ethical guidelines
All ethical principles in writing were observed according to the instructions of the National Ethics Committee and the COPE regulations.

Funding
The authors have followed the criteria of the International Committee of Medical Journal Editors.

Authors' contributions
The authors have complied with the criteria of the International Committee of Medical Journal Editors (ICMJE).

Conflicts of interest
The authors declare no conflict of interest.

Acknowledgements
The authors express their gratitude to the Vice-Chancellor for Research and Technology of Shahid Rajaee Teacher Training University .
 

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