Anti-inflammatory properties of high-density lipoprotein

高密度脂蛋白(高密度脂蛋白)通过清除动脉细胞中多余的胆固醇来预防动脉粥样硬化。高密度脂蛋白也被认为是体内细胞炎症和脂质氧化的重要抑制因子。此外，炎症被认为可以将高密度脂蛋白转化为一种功能失调的形式，从而失去这些心脏保护作用，甚至可能是促炎的。两条重要的途径可能涉及氧化损伤和高密度脂蛋白中促氧化蛋白和抗氧化蛋白相对平衡的变化。 在获奖的头两年，PI完成了高度结构化的职业发展计划，为他过渡到完全独立的调查员做好准备。在此期间，他在同行评议的期刊上发表了五篇第一作者论文，直接回答了最初提案中提出的假设。重要的是，他在糖尿病患者中获得了强有力的初步数据，表明所提出的产生功能障碍的高密度脂蛋白的机制与病理生理学有关。PI与华盛顿大学的翻译研究人员合作，为开发一项以了解高密度脂蛋白在糖尿病心血管疾病中的作用为中心的研究计划奠定了基础。重要的是，建议的研究完全独立于他的导师的研究。他还接受了华盛顿大学的教职员工职位，医学部为他分配了独立的实验室空间和新成立的糖尿病和肥胖卓越中心的办公室。 在K99/R00奖项的下一阶段，PI将专注于两个主要目标：第一，建立一个以糖尿病和心血管疾病为中心的完全独立的研究计划。第二，为他的研究获得NIH的资金。长期目标是通过了解糖尿病和其他炎症条件下人类产生功能障碍的高密度脂蛋白的分子机制来对抗动脉粥样硬化。

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.