Atheroprotective Mechanisms of Borage and Echium Oils/John S. Parks

琉璃苣油和蓝蓟油的动脉粥样硬化保护机制/John S. Parks

• 批准号: 8007042
• 负责人: FLOYD H CHILTON
• 金额: $ 70.02万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8007042
• 关键词: 1-Phosphatidylinositol 3-Kinase; Abbreviations; Animal Model; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Antiatherogenic; Arterial Fatty Streak; Atherosclerosis; Attenuated; Blood; Borago; Botanicals; Cardiovascular Diseases; Cause of Death; Chronic Disease; Consumption; Diet; Dietary Intervention; Docosahexaenoic Acids; Echium; Eicosanoids; Eicosapentaenoic Acid; Enzymes; Fatty Acids; Fatty acid glycerol esters; Fish Oils; Fishes; Funding; Gene Expression; Genes; Goals; Health; Human; IL4 gene; In Vitro; Inflammation; Inflammatory; Inflammatory Response Pathway; Injection of therapeutic agent; Intake; Kinetics; Knockout Mice; Knowledge; Linoleic Acids; Linolenic Acids; Linseed Oil; Lipids; Lipoproteins; Low Density Lipoprotein Receptor; Macrophage Activation; Membrane Microdomains; Monocytosis; Mus; Nature; Oils; PPAR gamma; Pathway interactions; Peritoneal Macrophages; Pharmacologic Substance; Phenotype; Plasma; Polyunsaturated Fatty Acids; Population; Property; Prostaglandins; Relative (related person); Risk; Saturated Fatty Acids; Series; Severities; Source; Surface; TLR4 gene; Testing; Thioglycolates; Transactivation; United States; Universities; alpha-Linolenic Acid; atheroprotective; attenuation; borage oil; desaturase; design; disorder prevention; feeding; forest; gamma-Linolenic Acid; improved; in vivo; insight; macrophage; monocyte; palm oil; protein expression; saturated fat; stearidonic acid; trafficking

During the previous funding cycle of the Wake Forest Center for Botanical Lipids, we demonstrated that Echium oil (EO), a botanical oil enriched in stearidonic acid (18:4 w3), the immediate downstream product of the rate-limiting delta-6 desaturation of alpha-linolenic acid (18:3 w3), reduces plasma lipids, inflammation, and atherosclerosis as well as fish oil (FO), but we do not know the exact mechanisms for the protection. EO also contains 11% gamma-linolenic acid (GLA, 18:3 w6), which is the delta-6 desaturation product of linoleic acid (18:2 w6) and thus, can provide substrate for conversion to anti-inflammatory series 1 prostaglandin (PGEI). However, we do not know whether a botanical oil that is enriched in GLA, such as borage oil (BO; 25% GLA), is equally protective or less protective than EO. The goal of project 1 in the renewal application is to investigate whether EO and BO are equally atheroprotective and to determine anti-atherogenic mechanisms ofthese botanical oils. Our primary hypothesis is that both EO and BO will reduce atherosclerosis relative to palm oil (PO), by attenuating the rise of proinflammatory monocytes in blood and the trafficking of monocytes into atherosclerotic lesions (specific aim 1). Furthermore, we hypothesize that EO and BO will result in alternative activation of macrophages, relative to PO, resulting in less inflammatory macrophages (specific aim 2). Finally, we propose that the polyunsaturated fatty acid (PUFA)-induced macrophage alternative activation will occur through multiple mechanisms that include antagonism of proinflammatory gene transactivation, PPARgamma-dependent transactivation of anti-inflammatory genes, and PPARgamma-dependent transrepression of pro-inflammatory genes (specific aim 3). The proposed mechanistic studies should allow us to determine the best botanical oils or combinations to move into human trials to test for reduction of atherosclerosis risk and inflammation and to improve our basic information regarding the mechanism of action of botanical oils in chronic disease prevention.

在维克森林植物脂中心的前一个资金周期中，我们证明了 棕榈油(EO)是一种富含硬脂酸(18：4w3)的植物油，它的直接下游产品 限速的α-亚麻酸的β-6去饱和度(18：3w3)，降低血脂，炎症， 和动脉粥样硬化以及鱼油(FO)一样，但我们不知道确切的保护机制。道德操守 还含有11%的伽马-亚麻酸(GLA，18：3w6)，这是亚油酸的Delta-6脱饱和产物 酸(18：2w6)，因此可以为转化为抗炎系列1前列腺素提供底物 (PGEI)。然而，我们不知道富含GLA的植物油，如萝卜油(BO； 25%GLA)，与EO具有同等的保护作用或更弱的保护作用。续签申请中的项目1的目标是 研究EO和BO是否具有同等的动脉粥样硬化保护作用，并确定是否具有抗动脉粥样硬化作用 这些植物油的作用机理。我们的主要假设是，EO和BO都将减少 与棕榈油(PO)相关的动脉粥样硬化，其机制是通过抑制血液中促炎症单核细胞的升高和 单核细胞向动脉粥样硬化病变的运输(特定目标1)。此外，我们假设 与PO相比，EO和BO会导致巨噬细胞的交替激活，从而减少炎症 巨噬细胞(特异性靶点2)。最后，我们提出多不饱和脂肪酸(PUFA)诱导的 巨噬细胞的选择性激活将通过多种机制发生，包括拮抗 致炎基因反式激活，依赖PPARγ的抗炎基因反式激活， 和PPAR-γ依赖的促炎基因转录抑制(特定目标3)。建议数 机械学研究应该允许我们确定进入人类的最佳植物油或组合 为降低动脉粥样硬化风险和炎症以及改善我们的基本信息而进行的试验 关于植物油在慢性病预防中的作用机制。