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. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL086224-02
Application #
7346990
Study Section
Special Emphasis Panel (ZRG1-F10-H (20))
Program Officer
Meadows, Tawanna
Project Start
2006-09-22
Project End
2008-06-30
Budget Start
2007-09-22
Budget End
2008-06-30
Support Year
2
Fiscal Year
2007
Total Cost
$41,912
Indirect Cost
Name
Stanford University
Department
Surgery
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305