GENETIC DETERMINATION OF ALLOGRAFT VASCULOPATHY

描述 (根据申请者摘要改编)本扎博士将成为助理 1997年4月，心血管病学部医学教授 (DCD)阿拉巴马大学(UAB)。本扎博士的专科训练 是心脏移植领域的研究人员，对 血管生物学。他获得了多个杰出的部门奖 他在内皮细胞介导的纤溶方面的研究，并介绍了他的 在几次国内和国际会议上进行研究。他收到了一份 美国心脏协会/阿拉巴马州会员奖 奖学金资助他在内皮细胞介导的纤溶和 在同行评议的期刊上发表了几篇文章。 他提议的研究将定义受损人群之间的关系 纤溶活性与心脏移植物血管病变的发生发展 (TX CAD)，这是移植后经常出现且代价高昂的问题。前提是 这些研究中的一项是TX CAD的发展可能与 某些纤溶蛋白(t-PA、PAI-1、u-PA)基因的存在 供体移植物和受体均存在多态现象(FPGP)。具体来说， 这些基因的表达可能会以特定于基因型的方式受到影响。 由某些因素(高甘油三酯血症)引起的 移植。这种纤溶蛋白(FP)的表达变化将 然后导致纤维蛋白沉积和类似TX的CAD的发展 本土化CAD的发展。在这方面，t-PA、PAI-1、u-PA的FPGP 纤维蛋白原将通过Southern印迹和聚合酶链式反应技术检测 150对捐赠者/受赠者。然后，这些患者将被追踪一段时间 为期4年，以确定这些FPGP是否可以预测 TX CAD的开发。此外，血浆水平(受体)和组织 FFP水平(活组织标本)将通过酶联免疫吸附试验和 分别进行免疫细胞化学荧光染色，以确定 这些蛋白的表达与纤溶基因类型之间存在联系 和TX CAD。 UAB、医学部和DCD将提供研究空间， 设施、资源(秘书支助和办公场所)和适当 时间承诺(80%)，以允许候选人进行和完成 本申请中提出的研究目标。他不会有任何 在本申请期内担任行政或教学职务。如果 他的教职员工导师即将离开学校，新的导师将 被任命并继续发展成为一名独立的 支持和鼓励内科科学家。

DESCRIPTION (Adapted from applicants' abstract) Dr. Benza will become an Assistant Professor of Medicine in April 1997, in the Division Cardiovascular Diseases (DCD) at the University of Alabama (UAB). Dr. Benza's subspecialty training is in the area of Cardiac Transplantation with a research interest in vascular biology. He has won several distinguished departmental awards for his research in endothelial cell-mediated fibrinolysis and has presented his research at several national and international meetings. He received an American Heart Association/Alabama Affiliate Award during his first year of fellowship to fund his work in endothelial cell-mediated fibrinolysis and has several publications in peer reviewed journals. His proposed studies will define the relationship between impaired fibrinolytic activity and the development of cardiac allograft vasculopathy (Tx CAD), a frequent and costly problem post transplantation. The premise of these studies is that the development of Tx CAD may be related to the presence of certain fibrinolytic protein (t-PA, PAI-1, u-PA) gene polymorphisms (FPGP) in both the donor graft and recipient. Specifically, the expression of these genes may be affected in a genotype-specific manner by certain factors (hypertriglyceridemia) which develop as a result of the transplant. This altered expression of fibrinolytic proteins (FPs) will then lead to fibrin deposition and the development of Tx CAD analogous to the development of native CAD. In this context, FPGPs for t-PA, PAI-1, u-PA and fibrinogen will be determined by Southern blot and PCR techniques for 150 donor/recipient pairs. These patients will then be followed for a period of 4 years to determine if these FPGP are predictive for the development of Tx CAD. In addition, plasma levels (recipient) and tissue levels (biopsy specimens) of FPs will be determined by ELISA and immuncytochemical fluorescent staining, respectively, to determine whether a link exists between the expression of these proteins, fibrinolytic genotypes and TX CAD. UAB, Department of Medicine and DCD will provide the research space, facilities, resources (secretarial support and office space) and appropriate time commitment (80%) 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 mentor were to leave the institution, a new mentor will be appointed and his continued development toward becoming a independent physician scientist supported and encouraged.