Aberrant Expression and Regulatory Role of Histone Deacetylase 9 in Vascular Endothelial Cell Injury in Intracranial Aneurysm

Overview

Journal Biomol Biomed

Specialties Biochemistry
General Medicine

Date 2023 Aug 13

PMID 37573538

Authors

Jingwei Sun

Langfeng Zhang

Quanjiang Cheng

Yajun Wu

Affiliations

Soon will be listed here.

Abstract

Intracranial aneurysm (IA) is one of the most challenging cerebrovascular lesions for clinicians. The aim of this study was to investigate the abnormal expression and role of histone deacetylase 9 (HDAC9) in IA-associated injury of vascular endothelial cells (VECs). First, IA tissue and normal arterial tissue were collected and VECs were isolated from IA patients. The expression levels of HDAC9, microRNA (miR)-34a-5p, and vascular endothelial growth factor-A (VEGFA) were determined. Cell viability, proliferation, apoptosis, and migration were assessed by Cell Counting Kit-8 (CCK-8) assay, EdU staining, TUNEL staining, and transwell assay. The binding of miR-34a-5p to VEGFA was analyzed by the dual-luciferase assay, and the accumulation of HDAC9 and lysine histone acetylation at H3 (H3K9, H3K14, and H3K18) on the miR-34a-5p promoter was detected by the chromatin immunoprecipitation assay. The results showed that HDAC9 and VEGFA were increased and miR-34a-5p was decreased in IA tissues and cells. Silencing of HDAC9 inhibited apoptosis and increased viability, proliferation, and migration of VECs, whereas overexpression of HDAC9 exerted the opposite functions. HDAC9 accumulated at the miR-34a-5p promoter to decrease miR-34a-5p expression by reducing H3 locus-specific acetylation and further promoted VEGFA expression. Knockdown of miR-34a-5p or VEGFA overexpression reversed the protective role of HDAC9 silencing in VECs injury. In conclusion, our study suggests that HDAC9 may be a therapeutic target for IA.

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References

Ajiboye N, Chalouhi N, Starke R, Zanaty M, Bell R . Unruptured Cerebral Aneurysms: Evaluation and Management. ScientificWorldJournal. 2015; 2015:954954. PMC: 4471401. DOI: 10.1155/2015/954954. View

Li M, Jia Q, Chen T, Zhao Z, Chen J, Zhang J . The role of vascular endothelial growth factor and vascular endothelial growth inhibitor in clinical outcome of traumatic brain injury. Clin Neurol Neurosurg. 2016; 144:7-13. DOI: 10.1016/j.clineuro.2016.02.032. View

Liu P, Shi Y, Fan Z, Zhou Y, Song Y, Liu Y . Inflammatory Smooth Muscle Cells Induce Endothelial Cell Alterations to Influence Cerebral Aneurysm Progression via Regulation of Integrin and VEGF Expression. Cell Transplant. 2018; 28(6):713-722. PMC: 6686430. DOI: 10.1177/0963689718815824. View

Sticht C, de la Torre C, Parveen A, Gretz N . miRWalk: An online resource for prediction of microRNA binding sites. PLoS One. 2018; 13(10):e0206239. PMC: 6193719. DOI: 10.1371/journal.pone.0206239. View

Chen M, Cheng H, Chen X, Gu J, Su W, Cai G . The activation of histone deacetylases 4 prevented endothelial dysfunction: A crucial mechanism of HuangqiGuizhiWuwu Decoction in improving microcirculation dysfunction in diabetes. J Ethnopharmacol. 2023; 307:116240. DOI: 10.1016/j.jep.2023.116240. View

Gao G, Zhang Y, Yu J, Chen Y, Gu D, Niu C . Long Non-coding RNA MALAT1/microRNA-143/VEGFA Signal Axis Modulates Vascular Endothelial Injury-Induced Intracranial Aneurysm. Nanoscale Res Lett. 2020; 15(1):139. PMC: 7324453. DOI: 10.1186/s11671-020-03357-2. View

Wang K, Jing Y, Xu C, Zhao J, Gong Q, Chen S . HIF-1α and VEGF Are Involved in Deferoxamine-Ameliorated Traumatic Brain Injury. J Surg Res. 2019; 246:419-426. DOI: 10.1016/j.jss.2019.09.023. View

Tian F, Wang J, Zhang Z, Yang J . LncRNA SNHG7/miR-34a-5p/SYVN1 axis plays a vital role in proliferation, apoptosis and autophagy in osteoarthritis. Biol Res. 2020; 53(1):9. PMC: 7027214. DOI: 10.1186/s40659-020-00275-6. View

Li S, Wei X, He J, Cao Q, Du D, Zhan X . The comprehensive landscape of miR-34a in cancer research. Cancer Metastasis Rev. 2021; 40(3):925-948. DOI: 10.1007/s10555-021-09973-3. View

10.

Ma Y, Huang Y, Chen Y . miRNA‑34a‑5p downregulation of VEGFA in endometrial stem cells contributes to the pathogenesis of endometriosis. Mol Med Rep. 2017; 16(6):8259-8264. DOI: 10.3892/mmr.2017.7677. View

11.

Yuan X, Bian X, Wei W, Bao Q, Liu P, Jiang W . miR-34a regulates phenotypic modulation of vascular smooth muscle cells in intracranial aneurysm by targeting CXCR3 and MMP-2. Genet Mol Biol. 2021; 44(2):e20200124. PMC: 8075123. DOI: 10.1590/1678-4685-GMB-2020-0124. View

12.

Wang Z, Qin W, Yi F . Targeting histone deacetylases: perspectives for epigenetic-based therapy in cardio-cerebrovascular disease. J Geriatr Cardiol. 2015; 12(2):153-64. PMC: 4394331. DOI: 10.11909/j.issn.1671-5411.2015.02.010. View

13.

Bourassa M, Ratan R . The interplay between microRNAs and histone deacetylases in neurological diseases. Neurochem Int. 2014; 77:33-9. PMC: 4321688. DOI: 10.1016/j.neuint.2014.03.012. View

14.

Yan K, Cao Q, Reilly C, Young N, Garcia B, Mishra N . Histone deacetylase 9 deficiency protects against effector T cell-mediated systemic autoimmunity. J Biol Chem. 2011; 286(33):28833-28843. PMC: 3190691. DOI: 10.1074/jbc.M111.233932. View

15.

Rikhtegar R, Mosimann P, Rothaupt J, Mirza-Aghazadeh-Attari M, Hallaj S, Yousefi M . Non-coding RNAs role in intracranial aneurysm: General principles with focus on inflammation. Life Sci. 2021; 278:119617. DOI: 10.1016/j.lfs.2021.119617. View

16.

Cai Y, Huang D, Ma W, Wang M, Qin Q, Jiang Z . Histone deacetylase 9 inhibition upregulates microRNA-92a to repress the progression of intracranial aneurysm via silencing Bcl-2-like protein 11. J Drug Target. 2021; 29(7):761-770. DOI: 10.1080/1061186X.2021.1878365. View

17.

Texakalidis P, Sweid A, Mouchtouris N, Peterson E, Sioka C, Rangel-Castilla L . Aneurysm Formation, Growth, and Rupture: The Biology and Physics of Cerebral Aneurysms. World Neurosurg. 2019; 130:277-284. DOI: 10.1016/j.wneu.2019.07.093. View

18.

Xu Z, Li H, Song J, Han B, Wang Z, Cao Y . Meta-Analysis of Microarray-Based Expression Profiles to Identify Differentially Expressed Genes in Intracranial Aneurysms. World Neurosurg. 2016; 97:661-668.e7. DOI: 10.1016/j.wneu.2016.10.093. View

19.

Kuang X, Chen S, Lao J, Chen Y, Jia D, Tu L . HDAC9 in the Injury of Vascular Endothelial Cell Mediated by P38 MAPK Pathway. J Interferon Cytokine Res. 2021; 41(12):439-449. DOI: 10.1089/jir.2021.0050. View

20.

Shi W, Wei X, Wang Z, Han H, Fu Y, Liu J . HDAC9 exacerbates endothelial injury in cerebral ischaemia/reperfusion injury. J Cell Mol Med. 2016; 20(6):1139-49. PMC: 4882992. DOI: 10.1111/jcmm.12803. View