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学科主题: 临床医学
题名:
Effect of Angiotensin II on STAT3 mediated atrial structural remodeling
作者: Zheng, L. -Y.1; Zhang, M. -H.1; Xue, J. -H.1; Li, Y.1; Nan, Y.1; Li, M. -J.1; Wang, J.2; Du, X. -P.1
关键词: Atrial fibrillation ; Atrial structural remodeling ; Angiotensin II ; Signal Transducers and Activators of Transcription (STAT)
刊名: EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES
发表日期: 2014-08-01
卷: 18, 期:16, 页:2365-2377
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Pharmacology & Pharmacy
研究领域[WOS]: Pharmacology & Pharmacy
关键词[WOS]: METALLOPROTEINASE GENE-EXPRESSION ; CONVERTING ENZYME-INHIBITORS ; MYOCYTE CELL-DEATH ; IV COLLAGENASE ; HEART-FAILURE ; GELATINASE-A ; TRANSCRIPTIONAL ACTIVATION ; MATRIX METALLOPROTEINASE-2 ; MYOCARDIAL-INFARCTION ; VENTRICULAR MYOCYTES
英文摘要:

OBJECTIVE: Atrial fibrillation (AF) has been identified to contribute significantly to the morbidity and mortality of cardiovascular disease patients. The atrial structural remodeling is a hallmark of AF and the molecular mechanisms underlying this remain unclear. Hence the objective of the present study is to determine the role of angiotensin II (AngII)/Ang-II type 1 (AT1) receptor - STAT3 signaling pathway on - atrial structural remodeling.

MATERIALS AND METHODS: The method of this study involves incubation of atrial myocytes, with Ang-II, to increase the level of apoptosis expressions by Tunel assay and the expression of apoptosis related factors like caspase 3 and 8 release of cytochrome C from mitochondria to cytosol by western blot test after OGD pre-treatment.

RESULTS: Atrial myocytes were shown to simulate the ischemia, hypoxia and atrial fibrillation. When incubated with Ang-II, (inhibited by losartan) the improvement was observed in the expression of caspase-3 and caspase-8. Ang-II also significantly promoted the transfer of cytochrome C levels from the mitochondria to the cytoplasm and this transfer was observed to be inhibited by losartan and WP1066. Ang-II incubation showed improved transcriptions of collagens and MMP expressions in atrial fibroblasts. In cultured atrial myocytes and fibroblasts, Ang-II induced tyrosine and serine phosphorylation of STAT3 showing interaction with MMP1 and MMP2 and DNA promoter sequences in atrial fibroblasts. The complete sequence was observed to have an affinity to be inhibited by losartan and WP1066.

CONCLUSIONS: Ang-II/AT1 receptor/STAT3 is an important signaling pathway in the atrial structural remodeling, Ang-II enhances the apoptosis of atrial parenchyma and deposition of atrial ECM, which might contributes to atrial fibrillation.

语种: 英语
所属项目编号: 2011BHKZ005
项目资助者: Tianjin Binhai New Area of Medical Science and Technology Projects
WOS记录号: WOS:000352203200021
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52694
Appears in Collections:北京大学第一临床医学院_期刊论文

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作者单位: 1.Fifth Cent Hosp Tianjin, Tianjin, Peoples R China
2.Beijing Univ, Hosp 1, Beijing 100871, Peoples R China

Recommended Citation:
Zheng, L. -Y.,Zhang, M. -H.,Xue, J. -H.,et al. Effect of Angiotensin II on STAT3 mediated atrial structural remodeling[J]. EUROPEAN REVIEW FOR MEDICAL AND PHARMACOLOGICAL SCIENCES,2014,18(16):2365-2377.
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