Histone deacetylase 9 inhibition upregulates microRNA-92a to repress the progression of intracranial aneurysm via silencing Bcl-2-like protein 11

Abstract

Objective

Histone deacetylases (HDACs) have been revealed to be involved in cerebrovascular diseases, while the role of HDAC9 in intracranial aneurysm (IA) remains seldom studied. We aim to explore the role of the HDAC9/microRNA-92a (miR-92a)/Bcl-2-like protein 11 (BCL2L11) axis in IA progression.

Methods

Expression of HDAC9, miR-92a and BCL2L11 in IA tissues was assessed. IA rat models were established by ligation of left renal artery and common carotid artery, and the rats were respectively injected with relative plasmid vectors and/or oligonucleotides. The blood pressure was measured to estimate the IA degree, and the pathological changes were observed. The expression of matrix metalloproteinase (MMP)-2, MMP-9 and vascular endothelial growth factor (VEGF) was detected, and the levels of inflammatory factors were evaluated. Expression of apoptosis-related proteins, HDAC9, miR-92a and BCL2L11 was assessed.

Results

HDAC9 and BCL2L11 were upregulated while miR-92a was downregulated in IA clinical samples and rat models. HDAC9 inhibition or miR-92a elevation improved pathological changes and repressed apoptosis and expression of MMP-2, MMP-9, VEGF and inflammatory factors in vascular tissues from IA rats. Oppositely, HDAC9 overexpression or miR-92a reduction had contrary effects. miR-92a downregulation reversed the effect of silenced HDAC9 on IA rats.

Conclusion

HDAC9 inhibition upregulates miR-92a to repress the progression of IA via silencing BCL2L11.

Keywords:

• Intracranial aneurysm
• histone deacetylase 9
• microRNA-92a
• Bcl-2-like protein 11
• inflammation
• apoptosis

Acknowledgements

The authors acknowledge the reviewers for their helpful comments on this paper.

Disclosure statement

The authors declare that they have no conflicts of interest.