Grants and Contracts Details
Description
Reducing total dietary fat intake has been used as a method for reducing the risk of coronary heart
disease for decades, however, numerous studies have demonstrated that the type of fat may be more
important than the total amount of fat in the diet. Unsaturated fats, such as. n-3 and n-6 fatty acids are
thought to be anti-atherogenicwhereas saturated fatty acids with 14-16 carbon atoms (i.e., myristicacid and
palmitic acid) are considered to be pro-atherogenic. Saturated fatty acids are thought to be pro-atherogenic,
in part, by causing an increase in total plasma cholesterol levels. Although plasma cholesterol levels clearly
influence the development of atherosclerotic lesions cholesterol is only one factor in the multi-factorial
disease of atherosclerosis. Our preliminary studies demonstrate that saturated fatty acid can cause an
increase in atherosclerosis independent of changes in plasma cholesterol levels. The goal of this proposal is
to determine the mechanism whereby saturated fatty acid promotes atherosclerosis without altering plasma
cholesterol. The preliminary data suggest that a novel signaling mechanism exists for saturated fatty acids
that involve SR-BI, caveolin, AMP kinase, and eNOS which subsequently results in the generation of the proatherogenic
compound, peroxynitrite. Three specific aims are proposed.
Aim 1: To determine the domains within SR-BI that interact with saturated fatty acids and caveolin
and to determine the domain within caveolin that interacts with SR-BI.
Aim 2: To elucidate the residue(s) in caveolin that are phosphorylated and the domains within
caveolin and AMP kinase that interact.
Aim 3: To determine if an endothelial-specific caveolin null mouse is protected from saturated fatty
acid-induced peroxynitrite production and subsequently atherosclerosis.
Status | Finished |
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Effective start/end date | 3/15/06 → 8/19/10 |
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