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Published on: September 24, 2020
Sevoflurane attenuates myocardial ischemia/reperfusion injury by up-regulating microRNA-99a and down-regulating BRD4
Xiaomin Bie1, Jiying Ao1, Degang Zhu1
1Wuhan No 1 Hospital - Department of Anesthesiology - Wuhan (Hubei) - China.
Purpose:
It has been explored that sevoflurane (Sevo) is cardioprotective in myocardial ischemia/reperfusion injury (MI/RI) and mediates microRNA (miRNA) expression that control various physiological systems. Enlightened by that, the work was programmed to decode the mechanism of Sevo and miR-99a with the participation of bromodomain-containing protein 4 (BRD4).
Methods:
MI/RImodel was established on mice. MI/RI modeled mice were exposed to Sevo or injected with miR-99a or BRD4-related vectors to identify their functions in cardiac function, pathological injury, cardiomyocyte apoptosis, inflammation, and oxidative stress in MI/RI mice. MiR-99a and BRD4 expression in myocardial tissues were tested, and their relation was further validated.
Results:
MiR-99a was down-regulated, and BRD4 was up-regulated in MI/RI mice. Sevo up-regulated miR-99a to inhibit BRD4 expression in myocardial tissues of MI/RI mice. Sevo improved cardiac function, relieved myocardial injury, repressed cardiomyocyte apoptosis, and alleviated inflammation and oxidative stress in mice with MI/RI. MiR-99a restoration further enhanced the positive effects of Sevo on mice with MI/RI. Overexpression of BRD4 reversed up-regulation of miR-99a-induced attenuation of MI/RI in mice.
Conclusions:
The work delineated that Sevo up-regulates miR-99a to attenuate MI/RI by inhibiting BRD4.
Insights
Sevoflurane (Sevo) protects the heart from injury by increasing miR-99a levels, which in turn reduces BRD4 expression. This mechanism alleviates myocardial ischemia/reperfusion injury (MI/RI) in mice.
Area of Science:
- Cardiology
- Molecular Biology
- Pharmacology
Background:
- Sevoflurane (Sevo) exhibits cardioprotective effects against myocardial ischemia/reperfusion injury (MI/RI).
- MicroRNA (miRNA) expression is implicated in physiological regulation and potentially mediates Sevo's protective actions.
- Bromodomain-containing protein 4 (BRD4) is a potential regulator in cellular processes.
Purpose of the Study:
- To elucidate the mechanism by which Sevo exerts cardioprotection in MI/RI.
- To investigate the role of miR-99a and its interaction with BRD4 in Sevo-mediated cardioprotection.
- To understand the impact of Sevo, miR-99a, and BRD4 on cardiac function and injury markers.
Main Methods:
- Myocardial ischemia/reperfusion injury (MI/RI) mouse models were established.
- Mice were treated with Sevo, miR-99a vectors, or BRD4 vectors to assess functional and pathological outcomes.
- Expression levels of miR-99a and BRD4 in myocardial tissues were quantified and their relationship analyzed.
Main Results:
- MI/RI mice showed decreased miR-99a and increased BRD4 expression.
- Sevo treatment upregulated miR-99a and downregulated BRD4 in MI/RI mice.
- Sevo improved cardiac function, reduced myocardial injury, cardiomyocyte apoptosis, inflammation, and oxidative stress, effects further enhanced by miR-99a restoration and reversed by BRD4 overexpression.
Conclusions:
- Sevoflurane upregulates miR-99a to inhibit BRD4, thereby attenuating myocardial ischemia/reperfusion injury.
- This pathway highlights a novel mechanism for Sevo's cardioprotective effects.
- Targeting the miR-99a/BRD4 axis may offer therapeutic strategies for MI/RI.
