Atherosclerosis is now widely recognized as a chronic inflammatory disease involving a complex interplaybetween resident vascular endothelial and smooth muscle cells and infiltrating immune cells, particularlymacrophages. An underlying hypothesis of this work is that inflammation can be modulated at thetranscriptional level by nuclear receptors and their co-repressors. Previous studies in our laboratoryidentified PPARd as an 'inflammatory switch' within the macrophage, in which ligands act to control theconcentrations of free and nuclear receptor-bound fractions of the co-repressors BCL-6 and SMRT.Biochemical, molecular, genetic, and physiologic approaches will be used to uncover the roles for thesefactors in inflammation and atherosclerosis. Finally, we will examine functions for PPARs throughout theartery wall and atherosclerotic lesion by utilizing conditional knockout models of PPARg and PPARd in thevascular endothelium. Studies will include both molecular and cell biology experiments and in vivoexperiments, taking advantage of unique nuclear receptor knockout and conditional knockout-derived cellsand mouse models using newly developed orally active PPARd-specific drugs along with the available classof PPARg therapeutics

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
1P01HL088093-01A1
Application #
7456188
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
2008-05-15
Project End
2013-03-31
Budget Start
2008-05-15
Budget End
2009-03-31
Support Year
1
Fiscal Year
2008
Total Cost
$492,375
Indirect Cost
Name
University of California San Diego
Department
Type
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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