التفاصيل البيبلوغرافية
| العنوان: |
VPO1 Modulates Vascular Smooth Muscle Cell Phenotypic Switch by Activating Extracellular Signal‐regulated Kinase 1/2 (ERK 1/2) in Abdominal Aortic Aneurysms |
| المؤلفون: |
Huihui Peng, Kai Zhang, Zhaoya Liu, Qian Xu, Baiyang You, Chan Li, Jing Cao, Honghua Zhou, Xiaohui Li, Jia Chen, Guangjie Cheng, Ruizheng Shi, Guogang Zhang |
| المصدر: |
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 7, Iss 17 (2018) |
| بيانات النشر: |
Wiley, 2018. |
| سنة النشر: |
2018 |
| المجموعة: |
LCC:Diseases of the circulatory (Cardiovascular) system |
| مصطلحات موضوعية: |
abdominal aortic aneurysm, hydrogen peroxide, oxidative stress, Diseases of the circulatory (Cardiovascular) system, RC666-701 |
| الوصف: |
Background Hydrogen peroxide (H2O2) is a critical molecular signal in the development of abdominal aortic aneurysm (AAA) formation. Vascular peroxidase 1 (VPO1) catalyzes the production of hypochlorous acid (HOCl) from H2O2 and significantly enhances oxidative stress. The switch from a contractile phenotype to a synthetic one in vascular smooth muscle cells (VSMCs) is driven by reactive oxygen species and is recognized as an early and important event in AAA formation. This study aims to determine if VPO1 plays a critical role in the development of AAA by regulating VSMC phenotypic switch. Methods and Results VPO1 is upregulated in human and elastase‐induced mouse aneurysmal tissues compared with healthy control tissues. Additionally, KLF4, a nuclear transcriptional factor, is upregulated in aneurysmatic tissues along with a concomitant downregulation of differentiated smooth muscle cell markers and an increase of synthetic phenotypic markers, indicating VSMC phenotypic switch in these diseased tissues. In cultured VSMCs from rat abdominal aorta, H2O2 treatment significantly increases VPO1 expression and HOCl levels as well as VSMC phenotypic switch. In support of these findings, depletion of VPO1 significantly attenuates the effects of H2O2 and HOCl treatment. Furthermore, HOCl treatment promotes VSMC phenotypic switch and ERK1/2 phosphorylation. Pretreatment with U0126 (a specific inhibitor of ERK1/2) significantly attenuates HOCl‐induced VSMC phenotypic switch. Conclusions Our results demonstrate that VPO1 modulates VSMC phenotypic switch through the H2O2/VPO1/HOCl/ERK1/2 signaling pathway and plays a key role in the development of AAA. Our findings also implicate VPO1 as a novel signaling node that mediates VSMC phenotypic switch and plays a key role in the development of AAA. Clinical Trial Registration URL: www.chictr.org.cn. Unique identifier: ChiCTR1800016922. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
2047-9980 |
| Relation: |
https://doaj.org/toc/2047-9980 |
| DOI: |
10.1161/JAHA.118.010069 |
| URL الوصول: |
https://doaj.org/article/b29bae5b8676463898d4f60cee098702 |
| رقم الانضمام: |
edsdoj.b29bae5b8676463898d4f60cee098702 |
| قاعدة البيانات: |
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