ENDOTHELIAL CELL FIBRINOLYSIS INDUCED BY WINE PHENOLICS

Aikens博士将于1999年7月1日成为UAB心血管疾病部（DCD）的医学助理教授。Aikens博士的亚专业培训是在心脏病学领域，研究兴趣是血管生物学。 他因研究酒精对内皮细胞（EC）介导的纤维蛋白溶解的心脏保护作用而获得了多项杰出的部门奖，并在多个国家会议上发表了他的研究。他的建议将确定红葡萄酒酚类化合物和EC介导的纤维蛋白溶解持续增加之间的关系，这可能有助于部分心脏保护。由于CAD风险的降低归因于适度的红葡萄酒消费，这可能是由于乙醇和葡萄酒中酚类化合物的抗氧化潜力或其他作用的综合作用。 可以想象的是，所选的葡萄酒酚类化合物，白藜芦醇，槲皮素和儿茶素可能具有额外的性质，这可能会影响EC功能的长期，特别是纤维蛋白溶解，独立于其直接的短期抗氧化性能。 进行这些初步研究，以确定是否选择葡萄酒酚类物质可能，事实上，诱导表达的t-PA和/或u-PA，导致在一个显着的持续增加的表达EC纤溶活性。 葡萄酒酚诱导的表面局部EC纤溶活性增加（初步研究）可能会降低血栓形成的风险。 所选的葡萄酒酚类物质将通过增加表面定位的纤溶酶产生的催化效率而在EC纤溶中产生持续的长期（24小时）增加（配体结合）（目的1）由t-PA和u-PA基因表达的转录上调引起（转录运行，转染）（目的2），通过与PA启动子中的特异性顺式作用调控区结合的因子（启动子缺失分析）（目的3）。UAB，医学系和DCD将提供研究空间，设施，资源（秘书支持和办公空间）和适当的时间承诺（75%），以允许候选人进行和完成本申请中规定的研究目标。 在此申请期间，他将没有行政或教学职责。 如果他的教师赞助人离开该机构，将任命一个新的赞助人，并支持和鼓励他继续发展成为一名独立的医生，科学家。

Dr. Aikens will become an Assistant Professor of Medicine on July 1, 1999, in the Division of Cardiovascular Diseases (DCD) at UAB. Dr. Aikens s subspecialty training is in the area of Preventative Cardiology with a research interest in vascular biology. He has won several distinguished departmental awards for his research cardioprotective effects of alcohol on endothelial cell(EC)-mediated fibrinolysis and has presented his research at several national meetings. His proposal will define the relationship between red wine phenolic compounds and sustained increases of EC mediated fibrinolysis, which may contribute, in part, to cardioprotection. Since the reduced risk for CAD has been attributed to moderate red wine consumption, which may be due to the combined effects of ethanol and the antioxidant potential or other effects of phenolic compounds in wine. It is conceivable that selected wine phenolic compounds, resveratrol, quercetin and catechin may have additional properties which may affect EC function in the long-term, in particular fibrinolysis, independent of their direct short-term antioxidant properties. These preliminary studies were carried out to determine whether select wine phenolics may, in fact, induce the expression of either t-PA and/or u-PA, resulting in a significant sustained increased expression of EC fibrinolytic activity. Wine phenolic-induced increased surface-localized EC fibrinolytic activity (preliminary studies) may be expected to decrease thrombotic risk. Selected wine phenolics will exert a sustained long-term (24 h) increase in EC fibrinolysis by increasing the catalytic efficiency of surface-localized plasmin generation (ligand binding) (Aim 1) resulting from the transcriptional upregulation of t-PA and u-PA gene expression(transcription run-on, transfection)(Aim 2) through factor(s) that bind to specific cis-acting regulatory region(s) in the PAs promoters(promoter deletion analysis) (Aim 3). UAB, Department of Medicine and DCD will provide the research space, facilities, resources (secretarial support and office space) and appropriate time commitment (75 percent) to allow the candidate to conduct and accomplish the research goals set forth in this application. He will have no administrative or teaching duties during the period of this application. If his faculty sponsor were to leave the institution, a new sponsor will be appointed and his continued development toward becoming an independent physician, scientist will be supported and encouraged.