The applicant proposes to determine if augmentation of 7alpha-hydroxylase activity in the liver or ectopic expression of 7alpha-hydroxylase in macrophages has a favorable effect on atherogenesis in hyperlipidemic mice.
The first aim i s to determine how transgenic expression of 7alpha-hydroxylase in the liver of hyperlipidemic mice influences plasma lipoprotein levels and atherogenesis.
The second aim i s to determine if the transgenic expression of 7alpha-hydroxylase in macrophages of hyperlipidemic mice influences atherogenesis. In other studies, bone marrow of hyperlipidemic mice will be replaced with stem cells obtained from mice expressing a 7alpha-hydroxylase macrophage-specific transgene.
Bradshaw, Gary; Gutierrez, Alejandra; Miyake, Jon H et al. (2005) Facilitated replacement of Kupffer cells expressing a paraoxonase-1 transgene is essential for ameliorating atherosclerosis in mice. Proc Natl Acad Sci U S A 102:11029-34 |