ROLE OF LIPOTPROTEINS IN THE TRANSPORT AND ACTIO OF OXYLIPINS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这个项目将回答这样一个问题：脂蛋白是否以含氧脂肪酸的形式转运脂质信号？“这些项目扩展了我们以前的发现，即含氧脂肪酸或氧脂素被酰化成脂蛋白脂质。 氧脂素是强有力的炎症脂质介质，因此可能是众所周知的脂蛋白诱导的炎症的活性剂。 如果是这样的话，了解脂蛋白氧化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-氧脂是否来源于自氧化或通过将调节氧脂产生酶（例如考克斯、LOX和COX）活性的治疗与调节炎症（例如LPS）的治疗相结合而酶促产生。 第二个目的是询问脂蛋白-氧化脂质的存在是否具有任何重要的生物学效应，使用心血管疾病的两个替代终点：内皮细胞极性（内皮功能障碍的标志物）和心脏成纤维细胞胶原蛋白的产生（心脏纤维化的标志物）。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This project will answer 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).