ENDOTHELIAL CELL FIBRINOLYSIS INDUCED BY WINE PHENOLICS

Aikens博士将于1999年7月1日成为UAB心血管疾病部门（DCD）的医学助理教授。Aikens博士的亚专业培训是在预防心脏病学领域，研究兴趣是血管生物学。他的研究“酒精对内皮细胞（EC）介导的纤维蛋白溶解的心脏保护作用”获得了几个杰出的部门奖，并在几个国家会议上发表了他的研究成果。他的建议将定义红酒酚类化合物与EC介导的纤维蛋白溶解持续增加之间的关系，这可能在一定程度上有助于心脏保护。由于冠心病风险的降低归因于适度饮用红酒，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，某些葡萄酒酚类化合物，白藜芦醇，槲皮素和儿茶素可能具有额外的特性，这些特性可能会长期影响EC功能，特别是纤维蛋白溶解，而不依赖于它们直接的短期抗氧化特性。这些初步研究是为了确定精选葡萄酒酚类物质是否实际上可以诱导t-PA和/或u-PA的表达，从而导致EC纤维蛋白溶解活性的显著持续增加。酒酚诱导的表面局部EC纤维蛋白溶解活性的增加（初步研究）可能会降低血栓形成的风险。通过结合PAs启动子中特定顺式作用调控区域的因子（启动子缺失分析），通过增加表面定位的纤溶酶生成（配体结合）的催化效率（目的1），从而持续长期（24小时）增加EC纤维蛋白溶解（目的3）。UAB，医学部和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%），以允许候选人进行并完成本申请中规定的研究目标。在此申请期间，他将不会担任任何行政或教学职务。如果他的教师赞助人离开了这个机构，一个新的赞助人将被任命，他将继续发展成为一个独立的医生，科学家将得到支持和鼓励。

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.