Histone Demethylase JMJD2A Inhibition Attenuates Neointimal Hyperplasia in the Carotid Arteries of Balloon-Injured Diabetic Rats via Transcriptional Silencing: Inflammatory Gene Expression in Vascular Smooth Muscle Cells
Background/Aims: Diabetic patients suffer from severe neointimal hyperplasia following angioplasty. The epigenetic abnormalities are increasingly considered to be relevant to the pathogenesis of diabetic cardiovascular complications. But the epigenetic mechanisms linking diabetes and coronary resten...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Cell Physiol Biochem Press GmbH & Co KG
2015-09-01
|
Series: | Cellular Physiology and Biochemistry |
Subjects: | |
Online Access: | http://www.karger.com/Article/FullText/430390 |
id |
doaj-6c5025541fca4a858d0ac742a60cf426 |
---|---|
record_format |
Article |
spelling |
doaj-6c5025541fca4a858d0ac742a60cf4262020-11-24T22:10:08ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-09-0137271973410.1159/000430390430390Histone Demethylase JMJD2A Inhibition Attenuates Neointimal Hyperplasia in the Carotid Arteries of Balloon-Injured Diabetic Rats via Transcriptional Silencing: Inflammatory Gene Expression in Vascular Smooth Muscle CellsHu QiZhang JingWu XiaolinXu ChangwuHu XiaorongYang JianChen JingJiang HongBackground/Aims: Diabetic patients suffer from severe neointimal hyperplasia following angioplasty. The epigenetic abnormalities are increasingly considered to be relevant to the pathogenesis of diabetic cardiovascular complications. But the epigenetic mechanisms linking diabetes and coronary restenosis have not been fully elucidated. In this study, we explored the protective effect and underlying mechanisms of demethylases JMJD2A inhibition in balloon-injury induced neointimal formation in diabetic rats. Methods: JMJD2A inhibition was achieved by the chemical inhibitor 2,4-pyridinedicarboxylic acid (2,4-PDCA) and small interfering RNA (siRNA). In vitro, we investigated the proliferation, migration and inflammation of rat vascular smooth muscle cells (VSMCs) in response to high glucose (HG). In vivo, diabetic rats induced using high-fat diet and low-dose streptozotocin (35mg/kg) underwent carotid artery balloon injury. Morphometric analysis was performed using hematein eosin and immumohistochemical staining. Chromatin Immunoprecipitation (ChIP) was conducted to detect modification of H3K9me3 at inflammatory genes promoters. Results: The global JMJD2A was increased in HG-stimulated VSMCs and balloon-injured arteries of diabetic rats, accompanied by decreased H3K9me3. The inhibition of JMJD2A suppressed VSMCs proliferation, migration and inflammation induced by high glucose (HG) in vitro. And JMJDA2A inhibition attenuated neointimal formation in balloon-injured diabetic rats. The underlying mechanisms were relevant to the restoration of H3K9me3 levels at the promoters of MCP-1 and IL-6, and then the suppressed expression of MCP-1 and IL-6. Conclusion: The JMJD2A inhibition significantly attenuated neointimal formation in balloon injured diabetic rats via the suppression of VSMCs proliferation, migration, and inflammation by restoring H3K9me3.http://www.karger.com/Article/FullText/430390Vascular smooth muscle cellJMJD2ARestenosisNeointimal hyperplasiaDiabetesInflammation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hu Qi Zhang Jing Wu Xiaolin Xu Changwu Hu Xiaorong Yang Jian Chen Jing Jiang Hong |
spellingShingle |
Hu Qi Zhang Jing Wu Xiaolin Xu Changwu Hu Xiaorong Yang Jian Chen Jing Jiang Hong Histone Demethylase JMJD2A Inhibition Attenuates Neointimal Hyperplasia in the Carotid Arteries of Balloon-Injured Diabetic Rats via Transcriptional Silencing: Inflammatory Gene Expression in Vascular Smooth Muscle Cells Cellular Physiology and Biochemistry Vascular smooth muscle cell JMJD2A Restenosis Neointimal hyperplasia Diabetes Inflammation |
author_facet |
Hu Qi Zhang Jing Wu Xiaolin Xu Changwu Hu Xiaorong Yang Jian Chen Jing Jiang Hong |
author_sort |
Hu Qi |
title |
Histone Demethylase JMJD2A Inhibition Attenuates Neointimal Hyperplasia in the Carotid Arteries of Balloon-Injured Diabetic Rats via Transcriptional Silencing: Inflammatory Gene Expression in Vascular Smooth Muscle Cells |
title_short |
Histone Demethylase JMJD2A Inhibition Attenuates Neointimal Hyperplasia in the Carotid Arteries of Balloon-Injured Diabetic Rats via Transcriptional Silencing: Inflammatory Gene Expression in Vascular Smooth Muscle Cells |
title_full |
Histone Demethylase JMJD2A Inhibition Attenuates Neointimal Hyperplasia in the Carotid Arteries of Balloon-Injured Diabetic Rats via Transcriptional Silencing: Inflammatory Gene Expression in Vascular Smooth Muscle Cells |
title_fullStr |
Histone Demethylase JMJD2A Inhibition Attenuates Neointimal Hyperplasia in the Carotid Arteries of Balloon-Injured Diabetic Rats via Transcriptional Silencing: Inflammatory Gene Expression in Vascular Smooth Muscle Cells |
title_full_unstemmed |
Histone Demethylase JMJD2A Inhibition Attenuates Neointimal Hyperplasia in the Carotid Arteries of Balloon-Injured Diabetic Rats via Transcriptional Silencing: Inflammatory Gene Expression in Vascular Smooth Muscle Cells |
title_sort |
histone demethylase jmjd2a inhibition attenuates neointimal hyperplasia in the carotid arteries of balloon-injured diabetic rats via transcriptional silencing: inflammatory gene expression in vascular smooth muscle cells |
publisher |
Cell Physiol Biochem Press GmbH & Co KG |
series |
Cellular Physiology and Biochemistry |
issn |
1015-8987 1421-9778 |
publishDate |
2015-09-01 |
description |
Background/Aims: Diabetic patients suffer from severe neointimal hyperplasia following angioplasty. The epigenetic abnormalities are increasingly considered to be relevant to the pathogenesis of diabetic cardiovascular complications. But the epigenetic mechanisms linking diabetes and coronary restenosis have not been fully elucidated. In this study, we explored the protective effect and underlying mechanisms of demethylases JMJD2A inhibition in balloon-injury induced neointimal formation in diabetic rats. Methods: JMJD2A inhibition was achieved by the chemical inhibitor 2,4-pyridinedicarboxylic acid (2,4-PDCA) and small interfering RNA (siRNA). In vitro, we investigated the proliferation, migration and inflammation of rat vascular smooth muscle cells (VSMCs) in response to high glucose (HG). In vivo, diabetic rats induced using high-fat diet and low-dose streptozotocin (35mg/kg) underwent carotid artery balloon injury. Morphometric analysis was performed using hematein eosin and immumohistochemical staining. Chromatin Immunoprecipitation (ChIP) was conducted to detect modification of H3K9me3 at inflammatory genes promoters. Results: The global JMJD2A was increased in HG-stimulated VSMCs and balloon-injured arteries of diabetic rats, accompanied by decreased H3K9me3. The inhibition of JMJD2A suppressed VSMCs proliferation, migration and inflammation induced by high glucose (HG) in vitro. And JMJDA2A inhibition attenuated neointimal formation in balloon-injured diabetic rats. The underlying mechanisms were relevant to the restoration of H3K9me3 levels at the promoters of MCP-1 and IL-6, and then the suppressed expression of MCP-1 and IL-6. Conclusion: The JMJD2A inhibition significantly attenuated neointimal formation in balloon injured diabetic rats via the suppression of VSMCs proliferation, migration, and inflammation by restoring H3K9me3. |
topic |
Vascular smooth muscle cell JMJD2A Restenosis Neointimal hyperplasia Diabetes Inflammation |
url |
http://www.karger.com/Article/FullText/430390 |
work_keys_str_mv |
AT huqi histonedemethylasejmjd2ainhibitionattenuatesneointimalhyperplasiainthecarotidarteriesofballooninjureddiabeticratsviatranscriptionalsilencinginflammatorygeneexpressioninvascularsmoothmusclecells AT zhangjing histonedemethylasejmjd2ainhibitionattenuatesneointimalhyperplasiainthecarotidarteriesofballooninjureddiabeticratsviatranscriptionalsilencinginflammatorygeneexpressioninvascularsmoothmusclecells AT wuxiaolin histonedemethylasejmjd2ainhibitionattenuatesneointimalhyperplasiainthecarotidarteriesofballooninjureddiabeticratsviatranscriptionalsilencinginflammatorygeneexpressioninvascularsmoothmusclecells AT xuchangwu histonedemethylasejmjd2ainhibitionattenuatesneointimalhyperplasiainthecarotidarteriesofballooninjureddiabeticratsviatranscriptionalsilencinginflammatorygeneexpressioninvascularsmoothmusclecells AT huxiaorong histonedemethylasejmjd2ainhibitionattenuatesneointimalhyperplasiainthecarotidarteriesofballooninjureddiabeticratsviatranscriptionalsilencinginflammatorygeneexpressioninvascularsmoothmusclecells AT yangjian histonedemethylasejmjd2ainhibitionattenuatesneointimalhyperplasiainthecarotidarteriesofballooninjureddiabeticratsviatranscriptionalsilencinginflammatorygeneexpressioninvascularsmoothmusclecells AT chenjing histonedemethylasejmjd2ainhibitionattenuatesneointimalhyperplasiainthecarotidarteriesofballooninjureddiabeticratsviatranscriptionalsilencinginflammatorygeneexpressioninvascularsmoothmusclecells AT jianghong histonedemethylasejmjd2ainhibitionattenuatesneointimalhyperplasiainthecarotidarteriesofballooninjureddiabeticratsviatranscriptionalsilencinginflammatorygeneexpressioninvascularsmoothmusclecells |
_version_ |
1725809138782437376 |