Saturated Fatty Acid and Cardiovascular Disease
饱和脂肪酸与心血管疾病
基本信息
- 批准号:7208080
- 负责人:
- 金额:$ 35.56万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-03-15 至 2011-02-28
- 项目状态:已结题
- 来源:
- 关键词:5&apos-AMP-activated protein kinaseAcidsAntiatherogenicArterial Fatty StreakAtherosclerosisBindingBiological AssayBos taurusBreedingCarbonCardiovascular DiseasesCattleCaveolinsCell membraneCellsCholesterolCoronaryCoronary heart diseaseDataDevelopmentDietDietary FatsDiseaseEndothelial CellsFatty AcidsFatty acid glycerol estersFibrinogenGenerationsGoalsIntakeKnockout MiceLigandsLow Density Lipoprotein ReceptorMethodsModelingMusMutateMyristic AcidsNitric OxidePalmitic AcidsPeroxonitritePhosphorylationPlasmaProductionReactive Oxygen SpeciesRecruitment ActivityResearch PersonnelRiskSaturated Fatty AcidsSignal TransductionStandards of Weights and MeasuresSystemTestingThinkingUnsaturated Fatsadenylate kinasebasecaveolin 1feedingnovelprogramsreceptor
项目摘要
DESCRIPTION (provided by applicant): The central hypothesis to be tested in this proposal is that binding of saturated fatty acid to SR-BI activates AMP kinase which results in the production of eNOS-dependent peroxynitrite and subsequently an increase in atherosclerotic lesions. 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-atherogenic whereas saturated fatty acids with 14-16 carbon atoms (i.e., myristic acid 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 pro- atherogenic 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.
描述(由申请方提供):本提案中待检验的中心假设是饱和脂肪酸与SR-BI的结合激活AMP激酶,导致eNOS依赖性过氧亚硝酸盐的产生,随后增加动脉粥样硬化病变。几十年来,减少膳食脂肪总摄入量一直被用作降低冠心病风险的方法;然而,许多研究表明,脂肪的类型可能比饮食中脂肪的总量更重要。不饱和脂肪,例如n-3和n-6脂肪酸被认为是抗动脉粥样硬化的,而具有14 - 16个碳原子的饱和脂肪酸(即,肉豆蔻酸和棕榈酸)被认为是促动脉粥样硬化的。饱和脂肪酸被认为是促动脉粥样硬化的,部分原因是引起血浆总胆固醇水平升高。虽然血浆胆固醇水平明显影响动脉粥样硬化病变的发展,但胆固醇只是动脉粥样硬化多因素疾病中的一个因素。我们的初步研究表明,饱和脂肪酸可引起动脉粥样硬化的增加,而不依赖于血浆胆固醇水平的变化。这项建议的目的是确定饱和脂肪酸促进动脉粥样硬化而不改变血浆胆固醇的机制。初步数据表明,饱和脂肪酸存在一种新的信号传导机制,涉及SR-BI、小窝蛋白、AMP激酶和eNOS,其随后导致促动脉粥样硬化化合物过氧亚硝酸盐的产生。提出了三个具体目标。目标1:确定SR-BI内与饱和脂肪酸和小窝蛋白相互作用的结构域,并确定小窝蛋白内与SR-BI相互作用的结构域。目的2:阐明小窝蛋白磷酸化的残基以及小窝蛋白与AMP激酶相互作用的结构域。目标三:确定内皮特异性小窝蛋白基因敲除小鼠是否受到饱和脂肪酸诱导的过氧亚硝酸盐产生和随后的动脉粥样硬化的保护。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Eric J Smart其他文献
Eric J Smart的其他文献
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{{ truncateString('Eric J Smart', 18)}}的其他基金
Proteomic identification of diabetes biomarkers
糖尿病生物标志物的蛋白质组学鉴定
- 批准号:
7127983 - 财政年份:2006
- 资助金额:
$ 35.56万 - 项目类别:
Proteomic identification of diabetes biomarkers
糖尿病生物标志物的蛋白质组学鉴定
- 批准号:
7268126 - 财政年份:2006
- 资助金额:
$ 35.56万 - 项目类别:
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