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[克隆性造血对非血液系统疾病和衰老过程的影响]

[Influence of clonal hematopoiesis on non-hematological diseases and aging processes].

作者信息

Rieger Michael A

机构信息

Medizinische Klinik 2, Hämatologie/Onkologie, Klinikum der Goethe-Universität, Theodor-Stern-Kai 7, 60590, Frankfurt am Main, Deutschland.

Exzellenzcluster Cardio-Pulmonary Institute, Frankfurt am Main, Deutschland.

出版信息

Inn Med (Heidelb). 2022 Nov;63(11):1115-1125. doi: 10.1007/s00108-022-01409-6. Epub 2022 Oct 10.

Abstract

The occurrence of clonal hematopoiesis, caused by acquired somatic mutations of leukemia-associated genes in blood stem cells is very common in the population and increases with age. Besides an increased risk of developing myeloid neoplasms, an unexpected causal relationship between clonal hematopoiesis and cardiovascular diseases was recently discovered. Clonal hematopoiesis presents as a new independent and strong risk factor for cardiovascular diseases, such as atherosclerosis, coronary heart disease, heart failure, aortic valve stenosis and stroke, which from a medical perspective should no longer be ignored. Worldwide intensive research for associations of clonal hematopoiesis with other age-related and infectious diseases identifies increasingly more illnesses that are influenced by the presence of mutated blood cells. Current data describe a fatal vicious circle, initiated by somatic blood cell mutations, which accelerate the progression of associated diseases in a proinflammatory way and feed-back to hematopoiesis leading to a further enlargement of the mutated blood cell clone. First experimental treatment approaches to break this vicious circle are discussed here. The causal relationship and the underlying pathomechanisms are now at the center of research interest in order to rapidly establish risk stratification and therapeutic measures for the benefit of patients in the near future.

摘要

由造血干细胞中白血病相关基因的获得性体细胞突变引起的克隆性造血在人群中非常普遍,且随年龄增长而增加。除了发生髓系肿瘤的风险增加外,最近还发现了克隆性造血与心血管疾病之间意想不到的因果关系。克隆性造血是心血管疾病(如动脉粥样硬化、冠心病、心力衰竭、主动脉瓣狭窄和中风)的一个新的独立且强大的危险因素,从医学角度来看,这一因素不应再被忽视。全球范围内对克隆性造血与其他年龄相关疾病和传染病关联的深入研究发现,越来越多的疾病受到突变血细胞存在的影响。目前的数据描述了一个由体细胞血细胞突变引发的致命恶性循环,这种突变以促炎方式加速相关疾病的进展,并反馈至造血过程,导致突变血细胞克隆进一步扩大。本文讨论了打破这一恶性循环的首批实验性治疗方法。因果关系及潜在的发病机制目前是研究的重点,以便在不久的将来迅速建立风险分层和治疗措施,造福患者。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c59c/9549812/82b1f8b86d71/108_2022_1409_Fig1_HTML.jpg

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