Inhibited histone deacetylase 3 ameliorates myocardial ischemia-reperfusion injury in a rat model by elevating microRNA-19a-3p and reducing cyclin-dependent kinase 2.

Abstract

OBJECTIVE:

Over the years, the roles of microRNAs (miRNAs) and histone deacetylase 3 (HDAC3) in human diseases have been investigated. This study focused on the effect of miR-19a-3p and HDAC3 in myocardial ischemia-reperfusion (I/R) injury (MIRI) by targeting cyclin-dependent kinase 2 (CDK2).

METHODS:

The I/R rat models were established by coronary artery ligation, which were then treated with RGFP966 (an inhibitor of HDAC3), miR-19a-3p agomir or antagomir, or silenced CDK2 to explore their roles in the cardiac function, pathological changes of myocardial tissues, myocardial infarction area, inflammatory factors and oxidative stress factors in rats with MIRI. The expression of miR-19a-3p, HDAC3, and CDK2 was determined by RT-qPCR and western blot assay, and the interaction among which was also verified by online prediction, luciferase activity assay and ChIP assay.

RESULTS:

The results indicated that HDAC3 and CDK2 were upregulated while miR-19a-3p was downregulated in myocardial tissues of I/R rats. The inhibited HDAC3/CDK2 or elevated miR-19a-3p could promote cardiac function, attenuate pathological changes, inflammatory reaction, oxidative stress, myocardial infarction area and apoptosis of myocardial tissues. HDAC3 mediates miR-19a-3p and CDK2 is targeted by miR-19a-3p.

CONCLUSION:

Inhibited HDAC3 ameliorates MIRI in a rat model by elevating miR-19a-3p and reducing CDK2, which may contribute to the treatment of MIRI.

• Authors: Kaiyou Song, Lianting Li, Qingqing Quan, Yanjin Wei, Shunpeng Hu
• Journal: IUBMB life (IUBMB Life) Vol. 72 Issue 12 Pg. 2696-2709 (12 2020) ISSN: 1521-6551 [Electronic] England
• PMID: 33217223 (Publication Type: Journal Article)
• Copyright: © 2020 International Union of Biochemistry and Molecular Biology.

Chemical References

• MIRN19 microRNA, rat
• MicroRNAs
• Cdk2 protein, rat
• Cyclin-Dependent Kinase 2
• Histone Deacetylases
• histone deacetylase 3

Topics

• Animals
• Apoptosis
• Cyclin-Dependent Kinase 2 (antagonists & inhibitors)
• Gene Expression Regulation
• Histone Deacetylases (chemistry)
• Male
• MicroRNAs (genetics)
• Myocardial Reperfusion Injury (etiology, metabolism, pathology, prevention & control)
• Myocytes, Cardiac (physiology)
• Oxidative Stress
• Rats
• Rats, Sprague-Dawley