Mechanisms underlying caloric restriction-mediated resolution of atherosclerosis

热量限制介导的动脉粥样硬化解决机制

基本信息

批准号：
10677793
负责人：
Ada Weinstock
金额：
$ 24.9万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-05 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10677793
关键词：
Adipose tissue Affect Apoptosis Arterial Fatty Streak Arteries Atherosclerosis Blood Vessels Body Weight decreased Bone Marrow Caloric Restriction Cardiovascular Diseases Cardiovascular system Cause of Death Cell physiology Cells Cholesterol Chronic Circulation Data Development Diet Disease Disease Management Disease remission Emigrations Epigenetic Process Event Foundations Future Genetic Transcription Hematopoietic Hematopoietic System Hematopoietic stem cells High Fat Diet Human Immune Immunologics Inflammation Inflammatory Kinetics Macrophage Mediating Medical Metabolic Diseases Modification Molecular Morbidity - disease rate Mus Obese Mice Obesity Pathology Pathway interactions Phagocytosis Phase Phenotype Population Postdoctoral Fellow Process Proliferating Research Resolution Risk Factors Role Signal Transduction Testing Time Tissues Transplantation Work bone comorbidity efficacious intervention hematopoietic cell transplantation hypercholesterolemia monocyte mortality mouse model novel obesity development progenitor programs recruit single-cell RNA sequencing systemic inflammatory response

项目摘要

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.

项目摘要肥胖和动脉粥样硬化通常是合并症的疾病全世界。这些过程的特征是脂肪组织和脉管系统中的炎症这有许多病理生理途径。尽管肥胖和动脉粥样硬化的过程与与动脉粥样硬化有关对炎症进行了充分的研究，促进疾病解决和缓解的信号在很大程度上尚不清楚，特别是在伴随炎症的背景下。作为博士后研究员，我调查了如何肥胖相关炎症的分辨率会影响心血管疾病，并发现热量限制肥胖小鼠诱导的体重减轻会促进动脉粥样硬化的分辨率。基于这些令人兴奋的发现，我建议在AIM 1中评估热量限制对肥胖脂肪组织和造血的影响祖细胞以及是否可以转移由限制热量产生的促进的表型通过脂肪或造血细胞移植。在AIM 2中，我建议通过哪些热量限制会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解决。这项工作将揭示影响细胞和组织的新功能减肥过程中的动脉粥样硬化过程。此外，这些研究将确定可能针对脂肪组织和动脉粥样硬化相关的炎症的靶向治疗。