Department of Medicine, Hematology/Oncology, Goethe University Hospital, Frankfurt, Germany.
Institute for Cardiovascular Regeneration, Goethe University, Frankfurt, Germany; Partner Site Rhine-Main, German Center for Cardiovascular Research (DZHK), Berlin, Germany.
Exp Hematol. 2020 Mar;83:95-104. doi: 10.1016/j.exphem.2019.12.006. Epub 2019 Dec 29.
Cardiovascular diseases (CVDs) remain the leading cause of death worldwide. Many studies have provided evidence that both genetic and environmental factors induce atherosclerosis, leading thus to cardiovascular complications. Atherosclerosis is an inflammatory disease, and aging is strongly associated with the development of atherosclerosis. Recent experimental evidence suggests that clonal hematopoiesis (CH) is an emerging cardiovascular risk factor that contributes to the development of atherosclerosis and cardiac dysfunction and exacerbates cardiovascular diseases. CH is caused by somatic mutations in recurrent genes in hematopoietic stem cells, leading to the clonal expansion of mutated blood cell clones. Many of the mutated genes are known in the context of myeloid neoplasms. However, only some individuals carrying CH mutations develop hematologic abnormalities. CH is clearly age dependent and is not rare: at least 10%-20% of people >70 years old carry CH. The newly discovered association between myeloid leukemia-driver mutations and the progression of CVDs has raised medical interest. In this review, we summarize the current view on the contribution of CH in different cardiovascular diseases, CVD risk assessment, patient stratification, and the development of novel therapeutic strategies.
心血管疾病(CVDs)仍然是全球范围内的主要死亡原因。许多研究提供了证据,表明遗传和环境因素都会导致动脉粥样硬化,从而导致心血管并发症。动脉粥样硬化是一种炎症性疾病,衰老与动脉粥样硬化的发展密切相关。最近的实验证据表明,克隆性造血(CH)是一种新兴的心血管风险因素,可导致动脉粥样硬化和心脏功能障碍的发展,并加重心血管疾病。CH 是由造血干细胞中反复出现的基因突变引起的,导致突变血细胞克隆的克隆性扩张。许多突变基因在髓系肿瘤的背景下是已知的。然而,只有一些携带 CH 突变的个体出现血液学异常。CH 明显依赖于年龄,而且并不罕见:至少有 10%-20%的>70 岁的人携带 CH。最近发现的髓系白血病驱动突变与 CVDs 进展之间的关联引起了医学界的兴趣。在这篇综述中,我们总结了 CH 在不同心血管疾病中的作用、CVD 风险评估、患者分层以及新的治疗策略的发展的最新观点。