Park Eunbee, Evans Megan A, Walsh Kenneth
Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Hematovascular Biology Center, Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
J Cardiovasc Aging. 2024 Jan;4(1). doi: 10.20517/jca.2023.39. Epub 2023 Dec 31.
Clonal hematopoiesis (CH) is a prevalent condition that results from somatic mutations in hematopoietic stem cells. When these mutations occur in "driver" genes, they can potentially confer fitness advantages to the affected cells, 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 face long-term risks of all-cause mortality and age-associated diseases, including cardiovascular disease and hematological malignancies. While considerable research has focused on understanding the association between CH and these diseases, less attention has been given to exploring the regulatory factors that contribute to the expansion of the driver gene clone. This review focuses on the association between environmental stressors and inherited genetic risk factors in the context of CH development. A better understanding of how these stressors impact CH development will facilitate mechanistic studies and potentially lead to new therapeutic avenues to treat individuals with this condition.
克隆性造血（CH）是一种普遍存在的状况，由造血干细胞中的体细胞突变引起。当这些突变发生在“驱动”基因中时，它们可能会赋予受影响细胞适应性优势，导致克隆性扩增。虽然大多数突变细胞的克隆性扩增通常被认为是无症状的，因为它们不会影响总体血细胞数量，但CH携带者面临全因死亡率和与年龄相关疾病的长期风险，包括心血管疾病和血液系统恶性肿瘤。尽管大量研究集中于理解CH与这些疾病之间的关联，但对于探索促成驱动基因克隆扩增的调控因素关注较少。本综述聚焦于在CH发展背景下环境应激源与遗传风险因素之间的关联。更好地理解这些应激源如何影响CH发展将有助于进行机制研究，并可能带来治疗这种状况患者的新治疗途径。
