Clonal Hematopoiesis: From Macrovascular to Microvascular Disease.
Clonal Hematopoiesis: From Macrovascular to Microvascular Disease.
复制标题
克隆造血：从大血管到微血管疾病。
DOI：
10.1161/atvbaha.123.319197
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Walsh,Kenneth
中科院分区：
文献类型：
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作者：
Cochran,Jesse;Walsh,Kenneth
长期以来，衰老一直被认为是包括心血管疾病(CVD)在内的许多疾病的关键危险因素。尽管许多其他高龄并发症的发生率增加，但在调整了这些传统危险因素后，年龄仍然是CVD的一个独立和重要的危险因素。1最近，克隆性造血(CH)，一种与年龄相关的现象，被发现是这种附加风险的可能机制。在这一过程中，由于衰老、辐射或其他内在/外在压力，造血干或祖细胞会引起体细胞突变。当这些突变发生在被称为驱动基因的特定基因上时，它们可以赋予细胞选择性生长优势，使它们能够在竞争中胜过邻近细胞，并克隆扩张，以在骨髓中占据更大比例的群体。引起CH的常见突变驱动基因包括DNMT3A、TET2(10-11易位2)、JAK2、ASXL1、PPM1D和TP53。2这些驱动基因的突变也在所有的子代白细胞中保持，这会影响细胞的生物学，并经常导致更多的促炎表型。鉴于造血细胞的高周转率，最近的估计表明，每天产生近2.6×1011个细胞，3随着年龄的增加，可检测到的CH水平变得几乎无处不在也就不足为奇了。4重要的是，心血管疾病结局中的CH的相加风险与为每一种常规心血管疾病风险因素估计的单个风险相似，如果不大于的话。5.
Aging has long been recognized as a key risk fac-tor for many pathologies, including cardiovascular disease (CVD). Despite the increased incidence of many other comorbidities with advanced age, age still remains an independent and significant risk factor for CVD after adjustment for these conventional risk factors. 1 Recently, clonal hematopoiesis (CH), an age-related phenomenon, was uncovered as a possible mechanism for this additive risk. In this process, hematopoietic stem or progenitor cells incur somatic mutations as a consequence of aging, irradiation, or other intrinsic/extrinsic stresses. When these mutations occur in particular genes, referred to as driver genes, they can confer a selective growth advantage to the cell, allowing them to outcompete neighboring cells and clonally expand to account for a greater proportion of the population within the bone marrow. Commonly mutated driver genes that give rise to CH include DNMT3A, TET2 (ten-eleven translocation 2), JAK2, ASXL1, PPM1D, and TP53. 2Mutations in these driver genes are also maintained within all progeny leukocytes, which can affect the cell’s biology and frequently result in a more proinflammatory phenotype. Given the high turnover rate of hematopoietic cells, with recent estimates suggesting that nearly 2.6× 1011 cells are generated per day, 3 it is unsurprising that detectable levels of CH become nearly ubiquitous with advanced age. 4 Importantly, the additive risk of CH in CVD outcomes is similar to, if not greater than, the individual risks estimated for each of the conventional CVD risk factors. 5