Mouse models of atherosclerosis provide an opportunity to examine the role of particular genes inlesion initiation and progression, but the data from different published studies are often difficult tocompare. This is due to the use of different diets, analysis times (primarily very short times), sites ofanalysis, and the limitation of testing to a single mouse model. To address these problems, Core Awill use the same protocols for all mouse studies, utilize a diet the mimics the Th1 inflammatoryresponse observed in human disease, analyze multiple time points including very late stages oflesion development, and analyze 3 sites of lesion formation for all mice. It will centralize thegeneration and breeding of gene-knockout mice, and will perform bone-marrow transplants usingthese animals. The core laboratory has also recently developed a macrophage-specific retroviralvector that allows efficient transduction of hematopoietic stems cells that leads to gene expressionin lesion macrophages in vivo. All of the projects in this PPG will utilize these approaches to perturbinflammatory genes and ask how these changes alter the initiation and progression ofatherosclerotic lesions. The Core will also facilitate, coordinate and standardize sacrifice of allproject study animals, prepare and blind tissue for analysis, provide histological stains and allquantitative methods of analysis. The combined analyses using identical protocols will allow directcomparison of the effects of perturbation of different inflammatory gene products, includinginflammatory genes involved in the regulation of macrophage recruitment and activation andsurvival pathways.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
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Heart, Lung, and Blood Initial Review Group (HLBP)
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University of Washington
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Wight, Thomas N (2018) A role for proteoglycans in vascular disease. Matrix Biol 71-72:396-420
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