Mechanisms underlying caloric restriction-mediated resolution of atherosclerosis

项目摘要 肥胖和动脉粥样硬化常是导致大量发病率和死亡率的共病 国际吧这些过程的特征分别是脂肪组织和脉管系统中的炎症， 有许多共同的病理生理途径。尽管肥胖和动脉粥样硬化相关的潜在过程 炎症被很好地研究，促进疾病消退和缓解的信号在很大程度上是未知的， 特别是在伴随炎症消退的情况下。作为一名博士后研究员，我调查了 肥胖相关炎症的消退影响心血管疾病，并发现热量限制- 肥胖小鼠中诱导的体重减轻促进动脉粥样硬化的消退。基于这些令人兴奋的发现， 我在目标1中建议评估热量限制对肥胖脂肪组织和造血系统的影响。 以及热量限制产生的促消退表型是否可以转移 通过脂肪或造血细胞移植。在目标2中，我建议通过以下方式研究机制： 热量限制影响动脉粥样硬化病变的内容和组成， 动脉粥样硬化消退。这项工作将揭示细胞和组织的新功能， 动脉粥样硬化过程中的体重减轻。此外，这些研究将确定可能 靶向用于脂肪组织和动脉粥样硬化相关炎症的伴随治疗。

PROJECT SUMMARY Obesity and atherosclerosis are frequently comorbid conditions contributing to substantial morbidity and mortality worldwide. The processes are characterized by inflammation in the adipose tissue and vasculature, respectively, that share many pathophysiologic pathways. Although processes underlying obesity and atherosclerosis-related inflammation are well studied, the signals that promote disease resolution and remission are largely unknown, especially in the context of concomitant inflammation resolution. As a postdoctoral fellow, I investigated how resolution of obesity-related inflammation influences cardiovascular disease and found that caloric-restriction- induced weight loss in obese mice promotes resolution of atherosclerosis. Building upon these exciting findings, I propose in Aim 1 to evaluate the impact of caloric-restriction on obese adipose tissue and hematopoietic progenitors and whether the pro-resolving phenotype produced by to caloric-restriction can be transferred through adipose or hematopoietic cell transplantation. In Aim 2, I propose to investigate the mechanisms by which caloric-restriction influences the content and composition of atherosclerotic lesions and promotes atherosclerosis resolution. This work will reveal novel functions of cells and tissues that influence the atherosclerotic process in weight loss. Additionally, these studies will identify novel molecular pathways that may be targeted for the concomitant treatment of adipose tissue and atherosclerosis-related inflammation.