Effects of HMG-coA Reductase Pathway Inhibitors on GCAD

HMG-coA 还原酶途径抑制剂对 GCAD 的影响

• 批准号: 7158362
• 负责人: WILLIAM STEIN
• 金额: $ 5.14万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-22 至 2008-09-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7158362
• 关键词: G protein; HMG coA reductases; alkyltransferase; atorvastatin; bioluminescence; cardiovascular disorder prevention; chemoprevention; coronary disorder; geranyl compound; green fluorescent proteins; heart transplantation; immunopharmacology; laboratory mouse; microarray technology; morphometry; oxidoreductase inhibitor; postdoctoral investigator; squalene; transplant rejection

DESCRIPTION (provided by applicant): Chronic rejection is the leading cause of death in heart transplant patients, yet, no effective treatment exists. One therapy that has shown promise is the use of HMG-CoA reductase inhibitors (statins), but the mechanism by which they operate remains unclear. This proposal describes a research project designed to delineate the role of HMG-CoA reductase pathway inhibitors in the prevention of chronic rejection in a murine cardiac transplant model. In addition, this project will lead to a greater understanding of the pathways affected in the formation of chronic rejection. This will be done by employing a novel model of chronic rejection which relies on bioluminescence imaging. The project has four specific aims: (1) the development and validation of the FVB Luciferase-GFP (beta-actin) to C57BL/6 cardiac transplant model of chronic rejection; (2) determination of the ability of atorvastatin to decrease the degree of chronic rejection in the model; (3) analysis of the ability of specific HMG-CoA reductase pathway inhibitors to suppress chronic rejection in this model; and (4) examination of the intracellular pathways affected by inhibition of the HMG- CoA reductase pathway using gene microarrays.

描述（由申请人提供）：慢性排斥是心脏移植患者死亡的主要原因，但尚无有效治疗。一种表现出希望的疗法是使用HMG-COA还原酶抑制剂（他汀类药物），但是它们运行的​​机制仍不清楚。该建议描述了一个研究项目，旨在描述HMG-COA还原酶途径抑制剂在预防鼠心脏移植模型中慢性排斥中的作用。此外，该项目将对形成慢性排斥反应的影响的途径有更深入的了解。这将通过采用一种依赖生物发光成像的新型慢性排斥模型来完成。该项目具有四个特定的目的：（1）FVB荧光素酶-GFP（β-肌动蛋白）对C57BL/6慢性拒绝的心脏移植模型的开发和验证； （2）确定阿托伐他汀降低模型中慢性排斥程度的能力； （3）分析特定的HMG-COA还原酶途径抑制剂在该模型中抑制慢性排斥的能力； （4）检查使用基因微阵列抑制HMG-COA还原酶途径影响的细胞内途径。