课题基金 / 基金详情

Impact of Clonal Hematopoiesis on the Progression of Kidney Disease

Impact of Clonal Hematopoiesis on the Progression of Kidney Disease
克隆造血对肾脏疾病进展的影响
批准号:
10419907
负责人:
RAYMOND C. HARRIS
金额:
$74.05万
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
未结题
起止时间:
2022-04-20 至 2026-03-31

项目摘要

项目成果

RAYMOND C. HARRIS的其他基金

相似基金

相关文献

中文摘要
翻译
克隆性造血不确定电位(CHIP)是一种新发现的疾病,其特征是 遗传上不同的、增殖性克隆性白细胞群体的个体发育。芯片的普及率增加 随着年龄的增大,不仅与血液学癌症的风险有关,而且与纤维化、系统性 炎症和动脉粥样硬化性心血管疾病。基因芯片在小鼠体内的移植 克隆性白细胞导致动脉粥样硬化加速、心肌纤维化和克隆性组织直接渗透 巨噬细胞与刺激间质纤维化。 年龄是慢性肾脏疾病(CKD)的主要危险因素,这种疾病与加速 心血管疾病、过早死亡和进展为透析依赖。生物机制 对这种与年龄相关的风险的认识还不完全。最后一个常见的病理过程是 进展性CKD为肾小管间质纤维化,以炎性堆积为特征。 肾间质内有浸润物和成纤维细胞,肾小管上皮细胞永久性丧失。 肾小管间质纤维化也是急性肾损伤进展过程中的中心基础损害。 (Aki)到慢性病。 基于CHIP与动脉粥样硬化、肾间质炎症和纤维化之间的机制联系,我们 假设CHIP是CKD进展的一个新的生物学危险因素。为了检验这一假设,我们建议 在已建立的慢性肾脏病和急性肾功能衰竭队列中,确定CHIP与肾脏疾病进展的相关性。 同时,我们建议使用公认的慢性阻塞性肺疾病动物模型来描述潜在的因果机制。 和急性肾脏疾病。 克隆性白细胞作为慢性肾脏病进展的新机制将代表一种新的疾病 可以激励未来有针对性的干预措施的途径。
英文摘要
Clonal hematopoiesis of indeterminate potential (CHIP) is a newly recognized disorder characterized by the ontogenesis of a genetically distinct, proliferative clonal leukocyte population. The prevalence of CHIP increases with older age and is associated not only with risk of hematologic cancers, but with fibrosis, systemic inflammation, and atherosclerotic cardiovascular diseases. Recapitulation of CHIP in mice by transplantation of clonal leukocytes results in accelerated atherosclerosis, cardiac fibrosis and direct tissue infiltration of clonal macrophages and stimulation of interstitial fibrosis. Age is a dominant risk factor for chronic kidney disease (CKD), which is associated with accelerated cardiovascular disease, premature death, and progression to dialysis dependence. The biological mechanisms conferring this age-associated risk are incompletely understood. The final common pathologic process in progressive CKD is tubulointerstitial fibrosis, which is characterized by the accumulation of inflammatory infiltrates and fibroblasts within the kidney interstitium and permanent loss of tubular epithelial cells. Tubulointerstitial fibrosis also represents the central underlying lesion in the progression of acute kidney injury (AKI) to chronic disease. Based on mechanistic links between CHIP and atherogenesis, kidney interstitial inflammation, and fibrosis, we hypothesize that CHIP is a novel biological risk factor for CKD progression. To test this hypothesis, we propose to determine the associations of CHIP with kidney disease progression in established cohorts of CKD and AKI. In parallel, we propose to delineate potential causal mechanisms using recognized animal models of chronic and acute kidney disease. The identification of clonal leukocytes as a novel mechanism of CKD progression would represent a new disease pathway that could motivate future targeted interventions.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Impact of Clonal Hematopoiesis on the Progression of Kidney Disease
Organ Specific Project - Kidney
  • 批准号:
    10201589
  • 项目类别:
  • 资助金额:
    $115.85万
  • 财政年份:
    2018
  • 负责人:
    RAYMOND C. HARRIS
  • 依托单位:
Vanderbilt O'Brien Kidney Center-Administrative Core
Vanderbilt O'Brien Kidney Center
海外基金