潜能未定的克隆性造血:关于衰老、炎症与动脉粥样硬化的新认识

Clonal hematopoiesis of indeterminate potential:insights about aging,inflammation and atherosclerosis

潜能未定的克隆性造血(clonal hematopoiesis of indeterminate potential,CHIP)是一种由年龄相关体细胞突变所致、致病潜能未定的造血干细胞扩增。新近研究显示,CHIP与动脉粥样硬化疾病的发生密切相关,CHIP相关突变(如DNMT3A、TET2、JAK2等)可激活炎症相关信号通路(如NLRP3、AIM2炎症小体等),诱发局部炎症反应,促进动脉粥样硬化斑块的形成,对于抗炎药物的开发与应用有重要意义。本文拟从流行病学、分子机制和临床意义3个方面,探讨CHIP与衰老、炎症和动脉粥样硬化发病机制的关系。

Clonal hematopoiesis of indeterminate potential(CHIP)refers to clonal hematopoiesis driven by age-related somatic mutations with undetermined potential for hematologic malignancy.Recent studies suggest that CHIP plays an important role in the pathogenesis of atherosclerosis,as mutations of CHIP genes(e.g.,DNMT3A,TET2,JAK2)could activate inflammation signal pathways(e.g.,NLRP3,AIM2 inflammasomes),induce regional inflammatory response,thereby promoting the formation of atherosclerotic plaques,for which antiinflammatory medications could be effective and of great interest.The current review aims to discuss the interactions between CHIP,aging,inflammation and atherosclerosis from the perspectives of epidemiology,molecular mechanistic and clinical practice.