Mechanisms underlying caloric restriction-mediated resolution of atherosclerosis

项目总结 肥胖和动脉粥样硬化经常并存，导致相当大的发病率和死亡率。 全世界。这些过程的特征分别是脂肪组织和血管系统中的炎症， 它们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过程 炎症得到了很好的研究，促进疾病缓解和缓解的信号在很大程度上是未知的， 尤其是在伴随的炎症消退的情况下。作为博士后研究员，我研究了 肥胖相关炎症的解决会影响心血管疾病，并发现限制卡路里- 诱导肥胖小鼠体重减轻可促进动脉粥样硬化的消退。基于这些令人兴奋的发现， 在目标1中，我建议评估热量限制对肥胖脂肪组织和造血的影响。 前体细胞和TO热量限制产生的前分解表型是否可以转移 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来研究这些机制 哪种热量限制影响动脉粥样硬化病变的含量和组成，并促进 动脉粥样硬化消退。这项工作将揭示细胞和组织的新功能，这些功能影响 体重减轻中的动脉粥样硬化过程。此外，这些研究将确定新的分子途径，可能 针对脂肪组织和动脉粥样硬化相关炎症的同期治疗。

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.