ROLE OF LIPOTPROTEINS IN THE TRANSPORT AND ACTIO OF OXYLIPINS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 这个项目回答了这样一个问题：“脂蛋白是否以含氧脂肪酸的形式传递脂质信号？”这些项目扩展了我们之前的发现，即含氧脂肪酸，或氧化脂质，被酰化成脂蛋白脂质。氧化脂质是炎症的强有力的脂质介质，因此可能是众所周知的脂蛋白引起的炎症的活性物质。如果是这样的话，了解脂蛋白氧脂在炎症中的作用将有助于深入了解动脉粥样硬化和心血管疾病的发展。第一个目的是研究脂蛋白氧脂是来自自氧化还是通过结合调节氧脂产生酶的活性的处理(例如COX、LOX和CYP)和调节炎症的处理(例如脂多糖)来获得。第二个目的是利用心血管疾病的两个替代终点：内皮细胞极性(内皮功能障碍的制造者)和心脏成纤维细胞产生的胶原(心脏纤维化的标志)，询问脂蛋白氧脂的存在是否具有任何重要的生物学效应。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This project answers the question "do lipoproteins transport lipid signals in the form of oxygenated FAs?" The projects extends on our previous finding that oxygenated FAs, or oxylipins, are acylated into lipoprotein lipids. Oxylipins are powerful lipid mediators of inflamation and so may be active agents of the well known lipoprotein induced inflammation. If so, understanding the role of lipoprotein-oxylipins in inflammation would give insight into the development of atherosclerosis and cardiovascular disease. The first aim investigates whether the lipoprotein-oxylipins are derived from autoxidation or enzymatically by combining treatment that modulate the activity of oxylipin-producing enzymes (e.g. COX, LOX and CYP) with treatments that modulate inflammation (e.g. LPS). The second aim asks whether presence of lipoprotein-oxylipins have any important biological effects using two surrogate endpoints for cardiovascular disease: endothelial cell polarity (a makrer for endothelial dysfunction) and cardiac fibroblast production of collagen (a marker for cardiac fibrosis).