Atherosclerosis is common in humans with diabetes. The underlying mechanisms are not completely clear. Common genetic conditions such as heterozygous LPL deficiency could potentiall be involved. However, the exact role of LPL and atherosclerosis, especially in diabetic patients is uncertain. The long term objective of the application is to understand the mechanisms of premature atherosclerosis in diabetic patients The applicants have generated a mouse with heterozygous LPL deficiency. These heterozygous mice have been crossed with low density lipoprotein receptor knockout mice to generate double knockout mice. The investigators have demonstrated the feasibility of diet-induced atherosclerosis in these models, as well as the production of experimental diabetes. The studies proposed will test the hypothesis that genetic heterozygous LPL deficiency promotes atherosclerosis in diabetes. The application has the following Specific Aims: To determine the effects of the LPL deficient heterozygous state alone and in combination with the LDL receptor deficient phenotype on atherosclerosis in mice with streptozotocin-induced diabetes used as a model for Type-I diabetes. To define how the LPL deficient heterozygous state interacts with streptozotocin-induced diabetes to affect vascular wall gene expression and lipoprotein biology. To determine the effects of the LPL heterozygous deficient state alone and in combination with the LDL receptor knockout phenotype on atherosclerosis in mic with dietary-induced diabetes used as a model for Type-II diabetes. To define how the LPL heterozygous deficient state interacts with this model of diabetes to affect vascular wall gene expression and lipoprotein biology.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL058427-04
Application #
6389672
Study Section
Metabolism Study Section (MET)
Program Officer
Wassef, Momtaz K
Project Start
1998-04-01
Project End
2002-03-31
Budget Start
2001-04-01
Budget End
2002-03-31
Support Year
4
Fiscal Year
2001
Total Cost
$276,117
Indirect Cost
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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