Anti-inflammatory properties of high-density lipoprotein

高密度脂蛋白（HDL）通过清除动脉中多余的胆固醇来防止动脉粥样硬化 细胞HDL也被认为是细胞炎症和脂质的重要抑制剂 体内氧化。此外，已经提出炎症将HDL转化为功能失调的形式， 失去这些心脏保护作用，甚至可能是促炎性的。两个重要的途径可能 涉及氧化损伤和HDL中促氧化蛋白和抗氧化蛋白相对平衡的变化。 在该奖项的前两年，PI已经完成了高度结构化的职业发展计划， 让他准备好成为一名完全独立的调查员在此期间，他先后发表了五篇第一 在同行评审期刊上发表的作者论文，直接解决了原始论文中提出的假设。 提议重要的是，他在糖尿病患者中获得了强有力的初步数据， 产生功能障碍的HDL的机制是病理生理学相关的。协同 作为华盛顿大学的翻译研究人员，PI已经为开发一个 该研究项目的重点是了解HDL在糖尿病心血管疾病中的作用。重要的是， 所提议的研究完全独立于他的导师的研究。他还接受了一个教师 华盛顿大学和医学系的职位已经分配给他独立 实验室空间和办公室在新成立的糖尿病和肥胖卓越中心。 在K99/R00奖项的下一阶段，PI将专注于两个主要目标：首先，建立一个全面的 以糖尿病和心血管疾病为中心的独立研究项目。第二，获得NIH 资助他的研究。长期的目标是通过了解动脉粥样硬化的发生， 在患有糖尿病和其他疾病的人中产生功能失调的HDL的分子机制 炎性条件。

High-density lipoprotein (HDL) protects against atherosclerosis by removing excess cholesterol from arterial cells. HDL has also been proposed to function as an important Inhibitor of cellular inflammation and lipid oxidation in vivo. Moreover, inflammation has been proposed to convert HDL to a dysfunctional form that loses these cardioprotective effects and may even be pro-inflammatory. Two important pathways may Involve oxidative damage and changes in the relative balance of pro- and antioxidant proteins in HDL. During the first two years of the award, the PI has completed a highly structured career development plan to prepare him for transition to a fully independent investigator. During this time, he has published five first author papers in peer-reviewed journals, that have directly addressed the hypotheses raised in the original proposal. Importantly, he has obtained strong preliminary data in diabetic humans that the proposed mechanisms for generation of dysfunctional HDL are pathophysiologically relevant. In collaboration with translational investigators at the University of Washington, the PI has laid the groundwork for developing a research program centered on understanding the role of HDL in diabetic cardiovascular disease. Importantly, the proposed studies are completely Independent of that of his mentor. He also has accepted a faculty position with the University of Washington and the Department of Medicine has assigned him independent laboratory space and an office at the newly established Diabetes and Obesity Center of Excellence. During the next phase of the K99/R00 award, the PI will focus on two major goals: first, establishing a fully independent research program centered on diabetes and cardiovascular diseases. Second, obtaining NIH funding for his research studies. The long-term goal is to combat atherosclerosis by understanding the molecular mechanisms for generation of dysfunctional HDL in humans suffering from diabetes and other inflammatory conditions.