UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER AT DALLAS
Grant: $211,950 - National Institutes of Health - Jul. 20, 2009
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Award Description: Atherosclerosis is a disease of chronic inflammation of the arterial wall, resulting from complex interactions between modified lipoproteins, macrophages, T lymphocytes, endothelial, and smooth muscle cells. Complications of atherosclerosis such as myocardial infarction and stroke are the leading causes of mortality in developed countries. Studies over the past decades have revealed more than 100 genes that can influence the development of atherosclerotic lesions. Our long-term goal is to elucidate the transcriptional regulatory mechanisms that control expression of these genes. The NIH funded parent grant RO1HL1085749 focuses on studying the role of transcription factor FOXO4 in atherosclerosis. Our results indicate that FOXO4 protects mice against atherosclerosis as mice deficient for Foxo4 develop elevated levels of atherosclerosis. In this administrative supplemental support application, we propose two sets of experiments to further investigate the underlying cellular and molecular mechanisms for the enhanced susceptibility of Foxo4-null mice to atherosclerosis. These experiments will contribute to expediting the accomplishment of the overall goal of the project. In the first set experiments, we will test the hypothesis that circulating monocyte-derived macrophages and T cells are the major contributors to the increased atherosclerosis in Foxo4-null mice by performing immunohistochemistry and bone marrow transplant (BMT) experiments. In the second set experiments, we will perform microarray experiment in combination with quantitative real-time PCR using aortic cDNA samples from high-fat fed apoE/Foxo4 double null mice and apoE single null mice. This experiment will allow us to identify the potential molecular targets of Foxo4 that are involved in pathology of the disease development. Accomplish the experiments proposed here will help us to understand the cellular and molecular mechanism(s) underlying the development of FOXO4-regulated atherosclerosis.
Project Description: As defined in the award description field.
Jobs Summary: A post-doctoral fellow is hired to carry out the project described. (Total jobs reported: 1)
Project Status: Less Than 50% Completed
This award's data was last updated on Jul. 20, 2009. Help expand these official descriptions using the wiki below.
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