HDL, Inflammation and Atherosclerosis

高密度脂蛋白（HDL）在预防CVD中起着关键作用。炎症是 在动脉粥样硬化的发病机制中的重要性。慢性炎症导致变化 在HDL中[例如，载脂蛋白A-1（apo A-1）和对氧磷酶（PON 1）降低，SAA增加 和通过质谱鉴定的其他新蛋白质]。这些变化与一个 丧失其抗动脉粥样硬化的特性。炎症也可能导致动脉粥样硬化前的变化， HDL。我们假设炎症引起的HDL成分和功能变化 提供了炎症和动脉粥样硬化之间的重要联系。我们还假设， HDL组成的变化可能是指示氧化损伤存在的生物标志物 和/或动脉壁水平的动脉粥样硬化。为了验证这些假设，我们计划 确定炎症（急性和慢性）如何影响HDL的组成，功能和作用， 在小鼠中的动脉粥样硬化形成。接下来，我们将测试炎症减少炎症的机制。 动脉粥样硬化保护性HDL载脂蛋白apo A-l和PONl，并增加潜在的致动脉粥样硬化性 HDL中载脂蛋白SAA。第三，我们将确定是否局部过度表达， 巨噬细胞的炎症和抗炎蛋白存在于HDL影响启动 和/或高胆固醇血症小鼠模型中动脉粥样硬化的进展。最后我们将 确定慢性炎症是否改变了HDL的组成和功能特性， 人类以类似于小鼠的方式，以及HDL蛋白质组成的变化是否 氧化和/或动脉粥样硬化的标志物。 质谱方法。这些研究将为我们的长期研究提供重要信息。 目的是了解炎症、脂蛋白代谢和 动脉粥样硬化

High density lipoprotein (HDL) plays a critical role in preventing CVD. Inflammation is of central importance in the pathogenesis of atherosclerosis. Chronic inflammation leads to changes in HDL [e.g. decreased apolipoprotein A-l (apo A-l) and paraoxonase (PON1), and increased SAA and other novel proteins identified by mass spectrometry]. These changes are associated with a loss of its atheroprotective properties. Inflammation also may lead to pro-atherogenic changes in HDL. We hypothesize that compositional and functional changes in HDL induced by inflammation provides an important link between inflammation and atherosclerosis. We also hypothesize that changes in HDL composition may be biomarkers that indicate the presence of oxidative damage and/or atherosclerosis at the level of the artery wall. To test these hypotheses, we plan to determine how inflammation (acute and chronic) influences HDL composition, function and role in atherogenesis in mice. Next, we will test the mechanism by which inflammation reduces the atheroprotective HDL apolipoproteins apo A-l and PON1, and increases the potentially proatherogenic apolipoprotein SAA in HDL. Third, we will determine whether local over-expression by macrophages of inflammatory and anti-inflammatory proteins present in HDL affects the initiation and/or progression of atherosclerosis in a mouse model of hypercholesterolemia. Finally, we will determine whether chronic inflammation alters the composition and functional properties of HDL in humans in a manner similar to that in mice, and whether changes in HDL protein composition are markers of oxidation and/or atherosclerosis Many of these studies will involve the use of novel mass spectrometric approaches. These studies should provide important information to our longterm goal of understanding the relationship between inflammation, lipoprotein metabolism and atherosclerosis.