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

在维克森林植物脂质中心的上一个资助周期中，我们证明了， 蓝蓟油（EO），一种富含十八碳四烯酸（18：4 w3）的植物油，是蓝蓟油的直接下游产品。 α-亚麻酸的限速δ-6去饱和（18：3 W3），降低血浆脂质，炎症， 和动脉粥样硬化以及鱼油（FO），但我们不知道确切的保护机制。EO 还含有11%的γ-亚麻酸（GLA，18：3 w 6），其是亚油酸的δ-6去饱和产物 酸（18：2 W 6），因此，可以提供转化为抗炎系列1前列腺素的底物 （PGEI）。然而，我们不知道富含GLA的植物油，如琉璃苣油（BO; 25% GLA），具有与EO相同或更低的保护性。更新申请中项目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，并确定抗动脉粥样硬化 mechanisms机制ofthese botanical植物oil油.我们的主要假设是EO和BO都将减少 相对于棕榈油（PO），通过减弱血液中促炎性单核细胞的上升， 单核细胞进入动脉粥样硬化病变的运输（具体目标1）。此外，我们假设， 相对于PO，EO和BO将导致巨噬细胞的交替激活，从而导致炎症反应减少。 巨噬细胞（具体目标2）。最后，我们提出，多不饱和脂肪酸（PUFA）诱导的 巨噬细胞的替代性激活将通过多种机制发生， 促炎基因反式激活，抗炎基因的PPARgamma依赖性反式激活， 和促炎基因的PPARgamma依赖性反式阻遏（特异性目的3）。拟议 机制研究应该使我们能够确定最好的植物油或组合进入人体 测试降低动脉粥样硬化风险和炎症的试验，并改善我们的基本信息 关于植物油在慢性病预防中的作用机制。

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.