Somatic TET2 mutations in cardiac remodeling

摘要 随着时间的推移，体细胞DNA突变的积累是许多组织衰老的标志。然而， 体细胞突变在癌症以外的年龄相关疾病中的因果作用是一个有争议的问题。 心血管疾病(CVD)是老年人死亡的主要原因，在这一背景下仍未得到探索 个人。最近对人类的大型外显子组测序研究表明，衰老不可避免地与 随着造血系统中体细胞突变频率的增加，这提供了一个具有竞争力的 对突变细胞的生长有利，从而允许其克隆性扩增(克隆性造血)。出乎意料的是， 这些体细胞突变与较高的心血管相关死亡率有关， 暗示了以前不为人知的体细胞 骨髓源性细胞的突变 和CVD 。然而，这些体细胞突变与心血管疾病之间是否存在因果联系仍有待研究。 不清楚和潜在的潜在机制是完全未知的，这是 建议的研究。

ABSTRACT The accumulation of somatic DNA mutations over time is a hallmark of aging in many tissues. However, the causal role of somatic mutations in age-associated disorders other than cancer is a matter of debate, and remains unexplored in the setting of cardiovascular disease (CVD), the leading cause of death in elderly individuals. Recent large exome sequencing studies in humans have shown that aging is inevitably associated with an increased frequency of somatic mutations in the hematopoietic system, which provide a competitive growth advantage to the mutant cell and thus allow its clonal expansion (clonal hematopoiesis). Unexpectedly, these somatic mutations were associated with a higher rate of cardiovascular-related deaths, suggesting a previously unrecognized link between somatic mutations in bone marrow-derived cells and CVD . However, whether there is a causal connection between these somatic mutations and CVD remains unclear and the potential underlying mechanisms are completely unknown, and this is the scientific premise of the proposed research.