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T CELL AND EVOLUTION OF GENETIC ATHEROGENESIS


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Collapse abstract
Atherosclerosis is the underlying basis for the morbidity and death in about half of the American adult population. It is characterized by the progressive accumulation of cells, lipids, and extracellular matrix. Among the cells that accumulate in atherosclerotic plaques are cells of the immune system, in particular T cells and macrophages. This has led to the suggestion that inflammatory and immune mechanisms are involved in the development of atherosclerosis. This proposal is designed to address the question of the role of T cells and their gene products in this process. Apoprotein E (apoE) deficient mice are an immune competent mouse strain that spontaneously develops early as well as complex lesions throughout the aortic tree. These mice have been crossed with an immune incompetent mouse strain, recombination activating gene 2 deficient (RAG2) mice, that lack both t cells and B cells. The rate of development and progression or regression of atherosclerosis will be examined in these two mouse strains. The cellular and biochemical composition of the early fatty lesions and the more advanced lesions will be examined in detail. By adoptive transfer the role of individual T cell subtypes in lesion development and composition will be examined in the immune incompetent RAG2- apoE deficient mice. In addition, apoE or mutants of apoE will be expressed in the liver and specific arterial cells in order to examine the ability of these proteins to influence plasma lipids and lipoprotein profiles and the development and progression of atherosclerosis.
Collapse sponsor award id
R01HL056827

Collapse Biography 

Collapse Time 
Collapse start date
1997-05-01
Collapse end date
2002-04-30