权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

MECHANISMS OF ALCOHOL INDUCED ENDOTHELIAL FIBRINOLYSIS

酒精诱导内皮纤维蛋白溶解的机制

基本信息

批准号：
6509272
负责人：
FRANCOIS M BOOYSE
金额：
$ 38.17万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-09-17 至 2004-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6509272
关键词：
annexins cardiovascular disorder prevention chemical kinetics chemoprevention disease /disorder proneness /risk drug interactions ethanol fibrinolysis gene expression human tissue plasmin plasminogen plasminogen activator plasminogen activator inhibitors protein biosynthesis receptor tissue /cell culture vascular endothelium

项目摘要

DESCRIPTION: (Adapted from the Investigator's Abstract) Epidemiologic studies indicate that moderate alcohol consumption (1-2 drinks/day) reduces the risk of cardiovascular mortality and that this cardioprotective benefit may be mediated, in part, by an increase in fibrinolysis. Endothelial cells (ECs) synthesize t-PA, u-PA, PAI-1 and Receptors (Rs) for PA and plasminogen (Pmg) (PARs PmgRs) and maintain normal hemostasis and fibrinolysis by activating EC-bound Pmg through the regulated synthesis and complex interactions of these components. Alterations in these EC components /interactions by systemic factors, i.e. alcohol will promote either thrombosis or facilitate clot lysis. The investigators have shown that low ethanol (<0.1%) induces a biphasic short (<30 min) and long term sustained (12 hr) increase in cultured EC fibrinolysis. The overall goal of these revised studies is ti identify/define the molecular regulatory mechanism underlying low ethanol-induced effects on the activity, interaction, and expression of cultured human EC-produced components (Pas and Rs) resulting in rapid short vs sustained long term increases in EC-fibrinolytic activity. Studies will include kinetic analysis of short-(no Pas Rs synthesis ) vs long term (new Pas/Rs synthesis) EC-bound Pmg activation (Aim 1); binding activity (Kd, Bmax) and changes in u-PAR, t-PAR, and PmgRs mRNAs (using antisens probes for candidate Rs for t-PA [annexinII] and Pmg [annexin II and alpha -enolase] and RPAs), including determination of potential transcriptional regulation of these R types by ethanol (transcription run-on assay) (Aim 2) ; and finally identification of ethanol responsive regions in the promoter and 5-flanking regions of the t-PA and u-PA genes, including initial identication of their respective ethanol-inducible transcription factors (promoter deletion analysis, transient transfection, EMSA) (Aim 3). Results gleaned from these studies will provide significant new insights into our understanding of the mechanisms underlying the upregulation of EC-mediated fibrinolytic activity by low ethanol, at both, the molecular and gene levels. Increased EC-fibrinolysis will substantially decrease the risk for thrombosis, CAD and associated atherothrombotic events leading to MI and will provide a well defined molecular basis to explain, in part, the cardioprotective benefit and reduced risk of cardiovascular mortality associated withe moderate alcohol consumption.

描述：（改编自研究者摘要）流行病学

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Ethanol-induced increased surface-localized fibrinolytic activity in cultured human endothelial cells: kinetic analysis.

乙醇诱导培养的人内皮细胞表面局部纤溶活性增加：动力学分析。

DOI：
发表时间：
2001
期刊：
Alcoholism, clinical and experimental research.
影响因子：
0
作者：
Abou-Agag,LH;Tabengwa,EM;Tresnak,JA;Wheeler,CG;Taylor,KB;Booyse,FM
通讯作者：
Booyse,FM

Ethanol-induced up-regulation of candidate plasminogen receptor annexin II in cultured human endothelial cells.

乙醇诱导培养的人内皮细胞中候选纤溶酶原受体膜联蛋白 II 的上调。

DOI：
发表时间：
2000
期刊：
Alcoholism, clinical and experimental research
影响因子：
0
作者：
Tabengwa,EM;Abou-Agag,LH;Benza,RL;Torres,JA;Aikens,ML;Booyse,FM
通讯作者：
Booyse,FM

Ethanol-induced up-regulation of the urokinase receptor in cultured human endothelial cells.

乙醇诱导培养的人内皮细胞中尿激酶受体的上调。

DOI：
发表时间：
2001
期刊：
Alcoholism, clinical and experimental research
影响因子：
0
作者：
Tabengwa,EM;Grenett,HE;Benza,RL;Abou-Agag,LH;Tresnak,JK;Wheeler,CG;Booyse,FM
通讯作者：
Booyse,FM

Polyphyenolics increase t-PA and u-PA gene transcription in cultured human endothelial cells.

多酚类化合物可增加培养的人内皮细胞中 t-PA 和 u-PA 基因的转录。