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Wake Forest植物脂质中心的先前资金周期中，我们证明了这一点 Echium Oil（EO），一种富含硬脂酸的植物油（18：4 W3），是直接下游产品 α-6-6-6-6-6-6-α-6-α-6-6-丁酸（18：3 W3）的饱和度减少血浆脂质，炎症， 和动脉粥样硬化以及鱼油（FO），但我们不知道保护的确切机制。 EO 还含有11％γ-中苯甲酸（GLA，18：3 W6），这是亚油果的Delta-6去饱和产物 酸（18：2 W6），因此可以提供底物转化为抗炎系列1前列腺素 （PGEI）。但是，我们不知道是否富含GLA的植物油，例如Borage Oil（Bo; 25％GLA），比EO具有同样的保护性或更少的保护性。续订应用程序中项目1的目标是 研究EO和BO是否同样具有动脉保护性并确定抗动脉粥样硬化 这些植物油的机制。我们的主要假设是EO和BO都会减少 动脉粥样硬化相对于棕榈油（PO），通过减弱血液中促炎单核细胞的兴起 将单核细胞运输到动脉粥样硬化病变中（特定目标1）。此外，我们假设 相对于PO，EO和BO将导致巨噬细胞的替代激活，从而减少炎症 巨噬细胞（特定目标2）。最后，我们提出了多不饱和脂肪酸（PUFA）诱导的 巨噬细胞的替代激活将通过多种机制发生，包括 促炎基因反式激活，抗炎基因的ppargamma依赖性反式激活， 促炎基因的ppargamma依赖性转化（特定目标3）。提议 机械研究应使我们能够确定最佳的植物油或组合以进入人类 试验以测试减少动脉粥样硬化风险和炎症的试验，并改善我们的基本信息 关于植物油在慢性疾病预防中的作用机理。