北京大学医学部机构知识库
Advanced  
IR@PKUHSC  > 北京大学第二临床医学院  > 心血管内科  > 期刊论文
学科主题: 临床医学
题名:
Short-term withdrawal of simvastatin induces endothelial dysfunction in patients with coronary artery disease: A dose-response effect dependent on endothelial nitric oxide synthase
作者: Chen, Hong1,2; Ren, Jing-Yi1,2; Xing, Yan1,2; Zhang, Wan-Lei3; Liu, Xin1,2; Wu, Pei1,2; Wang, Ruo-Jie1,2; Luo, Yu1,2
关键词: Simvastatin ; Endothelial function ; Nitric oxide ; Coronary artery disease
刊名: INTERNATIONAL JOURNAL OF CARDIOLOGY
发表日期: 2009-01-24
DOI: 10.1016/j.ijcard.2007.10.044
卷: 131, 期:3, 页:313-320
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cardiac & Cardiovascular Systems
研究领域[WOS]: Cardiovascular System & Cardiology
关键词[WOS]: LOW-DENSITY-LIPOPROTEIN ; SMOOTH-MUSCLE-CELLS ; STATIN TREATMENT ; DISCONTINUATION ; ATORVASTATIN ; EXPRESSION ; THERAPY ; RATES
英文摘要:

Background: Patients with coronary artery disease (CAD) have impaired endothelial function. Simvastatin therapy has been demonstrated to significantly improve endothelial function in these patients. Although withdrawal of statins is a frequent problem in clinical practice, the effects after discontinuation of statins treatment on endothelial function in patients with CAD are largely unknown.

Objective: This study investigated the effects after withdrawal of simvastatin on brachial artery endothelial function in patients with CAD and the underlying mechanisms.

Methods: We recruited 30 patients with established CAD. They were treated with 20 mg simvastatin for 4 weeks. Endothelial dependent flow-mediated vasodilation (FMD) was assessed in the brachial artery using high-resolution ultrasound at baseline, 4 weeks during simvastatin treatment, and 1 week after termination of therapy. 20 healthy subjects were also studied as a control group. Furthermore, we investigated underlying mechanisms on human umbilical vein endothelial cells (HUVECs) confluent monolayers at passages 2-3. HUVECs were exposed to simvastatin. After 24 h cells were repeatedly washed to remove the drugs, and the conditioned mediums were collected at the indicated time points. The nitric oxide (NO) production and levels of eNOS mRNA after 24 h of withdrawal of statins were examined.

Results: (1) Abrupt discontinuation of simvastatin treatment leads to a rebound of serum total cholesterol (21.3%) and LDL cholesterol (18.2%) in patients within 1 week, but they were still lower than the baseline values (P<0.05 for each parameter). (2) A significant decreased of FMD (-59.3%) was observed in patients after discontinuation of simvastatin in 1 week, and furthermore, the FMD was even lower than the baseline levels (4.6% vs. 5.6%, P<0.05). The reduction of FMD was not correlated with the change of LDL cholesterol (r=-0.343, P=0.081). In contrast to the unchanged LDL cholesterol level, abrupt discontinuation of therapy caused a rapid and significant decrease in FMD from 10.6% to 5.2% in healthy subjects at day 1, but it returned to baseline levels within 1 week. (3) In HUVECs, a maximum decrease of nitrite levels (-80%) was observed at 6 h after stopping simvastatin treatment, which was below the control levels. 24 h after stopping 10(-5) mmol/L and 10(-6) mmol/L simvastatin treatment, eNOS mRNA expression decreased to - 71% and - 42% (P<0.05), respectively.

Conclusions: Abrupt withdrawal of simvastatin treatment not only acutely and completely abrogates its beneficial effects on endothelial function in patients with CAD, but also induced further vascular injury compared with pretreatment status, independent of cholesterol levels. The underlying mechanism of these negative effects may be related to the suppression of endothelial NO production, which are dose-dependent. (C) 2008 Published by Elsevier Ireland Ltd.

语种: 英语
所属项目编号: NSFC30240036
项目资助者: National Natural Science Foundation of China
WOS记录号: WOS:000262328700004
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58168
Appears in Collections:北京大学第二临床医学院_心血管内科_期刊论文

Files in This Item:

There are no files associated with this item.


作者单位: 1.Natl Nat Sci Fdn China, Beijing, Peoples R China
2.Peking Univ, Peoples Hosp, Dept Cardiol, Beijing 100871, Peoples R China
3.Peking Univ, Peoples Hosp, Dept Ultrasonog, Beijing 100871, Peoples R China

Recommended Citation:
Chen, Hong,Ren, Jing-Yi,Xing, Yan,et al. Short-term withdrawal of simvastatin induces endothelial dysfunction in patients with coronary artery disease: A dose-response effect dependent on endothelial nitric oxide synthase[J]. INTERNATIONAL JOURNAL OF CARDIOLOGY,2009,131(3):313-320.
Service
Recommend this item
Sava as my favorate item
Show this item's statistics
Export Endnote File
Google Scholar
Similar articles in Google Scholar
[Chen, Hong]'s Articles
[Ren, Jing-Yi]'s Articles
[Xing, Yan]'s Articles
CSDL cross search
Similar articles in CSDL Cross Search
[Chen, Hong]‘s Articles
[Ren, Jing-Yi]‘s Articles
[Xing, Yan]‘s Articles
Related Copyright Policies
Null
Social Bookmarking
Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit

Items in IR are protected by copyright, with all rights reserved, unless otherwise indicated.

 

 

Valid XHTML 1.0!
Copyright © 2007-2017  北京大学医学部 - Feedback
Powered by CSpace