克隆性造血与心力衰竭风险。
Evidence of Clonal Hematopoiesis and Risk of Heart Failure.
机构信息
Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
出版信息
Curr Heart Fail Rep. 2020 Oct;17(5):271-276. doi: 10.1007/s11897-020-00476-w.
PURPOSE OF REVIEW
Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by persistent clonal expansion of adult hematopoietic stem cells, which has been increasingly found to be associated with cardiovascular disease and adverse outcomes in heart failure. Here we outline emerging studies on the prevalence of CHIP, and its association with cardiovascular and heart disease.
RECENT FINDINGS
Previous genomic studies have found CHIP mutations to be associated with increased risks of arterial disease, stroke, and mortality. Murine studies exploring TET2, DNMT3A, and JAK2 mutations have shown changes in cellularity that decrease cardiac function after insult, as well as increase inflammasome activation. Mutations in driver genes are associated with worse clinical outcomes in heart failure patients, as a potential result of the proinflammatory selection in clonal hematopoiesis. Advances in the field have yielded therapeutic targets tested in recent clinical studies and may provide a valuable diagnostic of risk in heart failure.
目的综述
不确定潜能的克隆性造血（CHIP）的特征是成人造血干细胞的持续克隆性扩张，越来越多的研究发现其与心血管疾病和心力衰竭不良结局相关。本文概述了 CHIP 的流行率及其与心血管疾病和心脏病的关联的最新研究进展。
最近的发现
先前的基因组研究发现 CHIP 突变与动脉疾病、中风和死亡率的风险增加有关。探索 TET2、DNMT3A 和 JAK2 突变的小鼠研究表明，细胞数量的变化会在损伤后降低心脏功能，并增加炎症小体的激活。心力衰竭患者中驱动基因的突变与更差的临床结局相关，这可能是克隆性造血中促炎选择的结果。该领域的进展已经产生了在最近的临床研究中测试的治疗靶点，可能为心力衰竭提供有价值的风险诊断。
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