Inhibited HDAC3 or Elevated MicroRNA-494-3p Plays a Protective Role in Myocardial Ischemia-Reperfusion Injury via Suppression of BRD4.

Abstract

Increased histone deacetylase 3 (HDAC3) has been demonstrated to contribute to the pathogenesis of myocardial ischemia-reperfusion injury (MI/RI). Therefore, the goal of this study was to investigate how HDAC3 regulated MI/RI by mediating microRNA (miR)-494-3p/dromodomain-containing protein 4 (BRD4) axis. The MI/RI model was established by ligating the right anterior descending coronary artery. Cardiomyocytes from newborn mice were treated with hypoxia/reoxygenation (H/R). Gain-of-function and loss-of-function approaches were implemented to figure out the roles of miR-494-3p and HDAC3 in MI/RI. miR-494-3p, HDAC3, and BRD4 in myocardial tissues of mice with MI/RI and H/R-treated cardiomyocytes were detected. The relationships between miR-494-3p and HDAC3 and BRD4 were identified. Reduced miR-494-3p and upregulated HDAC3 and BRD4 exhibited in myocardial tissues of mice with MI/RI and H/R-treated cardiomyocytes. Inhibited HDAC3 or elevated miR-494-3p repressed the inflammation and apoptosis, improved cardiac function, and ameliorated myocardial injury in myocardial tissues of mice with MI/RI. Suppression of HDAC3 or elevation of miR-494-3p depressed inflammation and apoptosis and promoted cell viability of primary cardiomyocytes. miR-494-3p targeted BRD4. The study concludes that suppressed HDAC3 plays a protective role in MI/RI by upregulation of miR-494-3p and inhibition of BRD4, which could be helpful for MI/RI therapy.

• Authors: Wuyang Zheng, Qiang Xie, Ziguan Zhang, Jun Li, Lihuan Fang, Weihua Li
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 58 Issue 9 Pg. 4268-4279 (Sep 2021) ISSN: 1559-1182 [Electronic] United States
• PMID: 33982231 (Publication Type: Journal Article)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Brd4 protein, mouse
• Interleukin-1
• Interleukin-6
• MicroRNAs
• Mirn494 microRNA, mouse
• Nuclear Proteins
• Transcription Factors
• Tumor Necrosis Factor-alpha
• Histone Deacetylases
• histone deacetylase 3

Topics

• Animals
• Apoptosis (physiology)
• Disease Models, Animal
• Female
• Histone Deacetylases (metabolism)
• Inflammation (blood, metabolism)
• Interleukin-1 (blood)
• Interleukin-6 (blood)
• Mice
• MicroRNAs (metabolism)
• Myocardial Reperfusion Injury (blood, metabolism)
• Myocardium (metabolism)
• Myocytes, Cardiac (metabolism)
• Nuclear Proteins (metabolism)
• Transcription Factors (metabolism)
• Tumor Necrosis Factor-alpha (blood)