Cardioprotective Effect of Nec-1 in Rats Subjected to MI/R: Downregulation of Autophagy-Like Cell Death

Objective. Necrostatin-1 (Nec-1), an inhibitor of necroptosis, has been reported to protect against myocardial ischemia-reperfusion (MI/R) injury. However, the contribution of the potential antinecroptotic effect of Nec-1 on its infarct limitation and cardiac function improvement effects after MI/R...

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Bibliographic Details
Published in:Cardiovascular therapeutics 2021, Vol.2021, p.9956814-8
Main Authors: Wang, Liang, Lv, Xuebai, Tian, Jue, Wang, Xiaoliang, Wu, Ye, Liu, Hui Rong
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Autophagy
Biochemistry
Cardiac function
Cardiomyocytes
Cell Death
Coronary vessels
Creatine kinase
Down-Regulation
Heart
Heart attacks
Heart diseases
Humans
Imidazoles
Indoles
Investigations
Ischemia
Laboratory animals
Myocardial Reperfusion Injury - prevention & control
Myocytes, Cardiac
Rats
Rats, Sprague-Dawley
Reperfusion
Signal transduction
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Summary:Objective. Necrostatin-1 (Nec-1), an inhibitor of necroptosis, has been reported to protect against myocardial ischemia-reperfusion (MI/R) injury. However, the contribution of the potential antinecroptotic effect of Nec-1 on its infarct limitation and cardiac function improvement effects after MI/R has not been investigated. Methods. The present study investigated the effect of Nec-1 on myocardial infarct size, necroptosis, and cardiac functional recovery in rats subjected to myocardial ischemia-reperfusion (MI/R 30 min/12, 24, 48, and 72 h). Results. The study showed that Nec-1 might reduce myocardial cell death and maintain myoarchitectonic integrity, consequently inhibiting the reactive fibrosis process in rats in myocardial ischemia/late reperfusion. Moreover, the administration of Nec-1 (0.6 mg/kg) at the onset of reperfusion significantly reduced the release of creatine kinase and downregulation of autophagy within 24 h after reperfusion, and there was a significantly positive correlation between them. Conclusion. These results suggest that antinecroptosis treatment may improve the clinical outcomes of patients with ischemic heart disease.
ISSN:1755-5914
1755-5922
1755-5922
DOI:10.1155/2021/9956814