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.

在维克森林植物脂质中心之前的资助周期中，我们证明了这一点