This is the second renewal of this Program Project Grant, which has focused on the structure and function of key proteins in lipoprotein metabolism and atherosclerosis. During the next 5 years, our goals will be: 1) To identify the structural domains of apolipoproteins that regulate lipid transport; 2) To contribute to the understanding of the involvement of apo-B-containing lipoproteins in atherogenesis; and 3) To more fully understand the physiologic roles of lipoproteins and apolipoproteins in metabolism, including the roles of lipoproteins in embryonic development and in cardiac physiology. Four projects and four cores have been assembled, which interact closely and contribute significantly to each other. The research program is multi- disciplinary and relies on state-of-the-art technology, including X-ray crystallography, transgenic and gene-targeted mouse models, cellular biology, and ultrastructural biology. """"""""Influence of Apolipoprotein E structure on Function,"""""""" uses X-ray crystallography and biochemical approaches to determine the three- dimensional structure of apo-E and to determine how the three-dimensional structure affects lipoprotein metabolism. """"""""Cellular Mechanism for Lipoprotein Retention in the Artery Wall,"""""""" will test the hypothesis that proteoglycan binding sites in apo-B play a crucial role in the retention of lipoproteins in the artery wall and the development of atherosclerosis. """"""""Alpha-TTP and Vitamin E in Development and Disease,"""""""" explores the role alpha-tocopherol transfer protein and vitamin E in metabolism and atherosclerosis. The Cores (Animal Model; Histology, Atherosclerosis, Ultrastructure; Cell Culture and Protein Production; Administration) will provide the common services that are necessary for accomplishing the goals of the Program Project.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL041633-12
Application #
6151256
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
1989-02-01
Project End
2004-01-31
Budget Start
2000-02-01
Budget End
2001-01-31
Support Year
12
Fiscal Year
2000
Total Cost
$2,021,507
Indirect Cost
Name
J. David Gladstone Institutes
Department
Type
DUNS #
047120084
City
San Francisco
State
CA
Country
United States
Zip Code
94158
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