Clonal Hematopoiesis: Connecting Aging and Inflammation in Atherosclerosis.

Clonal Hematopoiesis: Connecting Aging and Inflammation in Atherosclerosis.
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DOI:
10.1007/s11883-023-01083-5
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发表时间:
2023-03
影响因子:
5.8
通讯作者:
Walsh, Kenneth
Walsh, Kenneth
中科院分区:
医学2区
文献类型:
--
作者:
Polizio, Ariel H.;Park, Eunbee;Walsh, Kenneth

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克隆性造血(CH)是由造血干细胞中获得体细胞突变引起的普遍病症。当这些突变发生在“驱动”基因中时,它们可能会赋予细胞适应性优势,导致克隆扩增。虽然大多数突变细胞的克隆扩增通常被认为是无症状的,因为它们不影响总体血细胞数量,但CH携带者显示出全因死亡和年龄相关疾病(包括心血管疾病(CVD))的长期风险。本文综述了CH与衰老、动脉粥样硬化性心血管疾病和炎症相关的最新研究结果,强调流行病学和机制研究,以及治疗CH促进的心血管疾病的潜在治疗方案。流行病学研究揭示了CH与心血管疾病之间的关联。采用Tet 2-和Jak 2-突变小鼠系的CH模型的实验研究显示炎性小体激活和慢性炎症状态,其导致加速的动脉粥样硬化病变生长。大量证据表明,CH代表了CVD的一个新的因果风险因素。研究还表明,了解个体的CH状态可以为使用抗炎药物治疗动脉粥样硬化和其他心血管疾病的个性化方法提供指导。
Clonal hematopoiesis (CH) is a prevalent condition that results from the acquisition of somatic mutations in hematopoietic stem cells. When these mutations occur in “driver” genes, they can potentially confer fitness advantages to the cell, leading to a clonal expansion. While most clonal expansions of mutant cells are generally considered to be asymptomatic since they do not impact overall blood cell numbers, CH carriers display long-term risks of all-cause mortality and age-associated diseases including cardiovascular disease (CVD). This review summarizes recent findings in CH related to aging, atherosclerotic CVD, and inflammation, emphasizing epidemiological and mechanistic studies, and potential therapeutic options to treat CVDs that are promoted by CH. Epidemiological studies have revealed associations between CH and CVDs. Experimental studies with CH models employing the Tet2- and Jak2-mutant mouse lines display inflammasome activation and a chronic inflammatory state that leads to accelerated atherosclerotic lesion growth. A body of evidence suggests that CH represents a new causal risk factor for CVD. Studies also indicate that understanding an individual’s CH status could provide guidance for personalized approaches to treat atherosclerosis and other CVDs with anti-inflammatory drugs.
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