美国哈佛医学院Kamila Naxerova研究组发现，动脉粥样硬化中干细胞增殖的增加加速了克隆性造血作用。2021年2月25日，《细胞》杂志在线发表了这一最新研究成果。

研究人员发现，在患有动脉粥样硬化的小鼠和人类中，造血干细胞的分裂速率增加。数学分析表明，增加的干细胞增殖可加速具有驱动程序突变的克隆的体细胞进化和扩增。实验表明，动脉粥样硬化患者的细胞分裂率升高足以使到70岁时的克隆性造血风险增加3.5倍。

通过证明在长期升高的造血活动条件下，竞争性移植的Tet2^-/-细胞的扩增会加速，研究人员证实了理论框架在动脉粥样硬化和睡眠破碎小鼠模型中的准确性。因此，造血干细胞增殖的增加是促成心血管疾病与克隆性造血之间联系的重要因素。 

研究人员介绍，克隆性造血是一种个体造血干细胞克隆产生不成比例的血液白细胞的状态，这与心血管疾病的较高风险相关。但这种关联背后的机制尚不完全清楚。

附：英文原文

Title: Increased stem cell proliferation in atherosclerosis accelerates clonal hematopoiesis

Author: Alexander Heyde, David Rohde, Cameron S. McAlpine, Shuang Zhang, Friedrich F. Hoyer, Jeffrey M. Gerold, David Cheek, Yoshiko Iwamoto, Maximilian J. Schloss, Katrien Vandoorne, Oriol Iborra-Egea, Christian Muoz-Guijosa, Antoni Bayes-Genis, Johannes G. Reiter, Morgan Craig, Filip K. Swirski, Matthias Nahrendorf, Martin A. Nowak, Kamila Naxerova

Issue&Volume: 2021-02-25

Abstract: Clonal hematopoiesis, a condition in which individual hematopoietic stem cell clonesgenerate a disproportionate fraction of blood leukocytes, correlates with higher riskfor cardiovascular disease. The mechanisms behind this association are incompletelyunderstood. Here, we show that hematopoietic stem cell division rates are increasedin mice and humans with atherosclerosis. Mathematical analysis demonstrates that increasedstem cell proliferation expedites somatic evolution and expansion of clones with drivermutations. The experimentally determined division rate elevation in atherosclerosispatients is sufficient to produce a 3.5-fold increased risk of clonal hematopoiesisby age 70. We confirm the accuracy of our theoretical framework in mouse models ofatherosclerosis and sleep fragmentation by showing that expansion of competitivelytransplanted Tet2/ cells is accelerated under conditions of chronically elevated hematopoietic activity.Hence, increased hematopoietic stem cell proliferation is an important factor contributingto the association between cardiovascular disease and clonal hematopoiesis.

DOI: 10.1016/j.cell.2021.01.049

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00092-1