Mosaic loss of Y chromosome in blood and heart failure

总结 最近的技术进展表明，体细胞DNA突变随着年龄的增长而积累， 普遍存在。血细胞中突变的积累与各种原因的增加有关。 死亡率和心脏代谢疾病。研究主要集中在癌前克隆性造血状态 这是由在血癌中反复突变的“驱动”基因突变引起的。然而，这类 突变代表了血液中发生的总体细胞嵌合现象的一小部分。Y染色体的镶嵌丢失 血液中的mLoY是人类最常见的合子后突变。流行病学研究 mLoY与全因死亡率和许多年龄相关疾病相关。但据 尚不清楚mLoY与心血管疾病之间是否存在因果关系。在这里，我们将 采用多种鼠模型评估mLoY对心力衰竭的影响，并研究这种关系 在机械的层面上。

SUMMARY Recent technological advances indicate that somatic DNA mutations accumulate with age and are remarkably prevalent. The accumulation of mutations in blood cells has been associated with increases in all-cause mortality and cardiometabolic diseases. Studies have focused on the precancerous clonal hematopoiesis state that results from mutations in “driver” genes that recurrently mutate in blood cancers. However, this class of mutations represent a small fraction of the total somatic mosaicism that occurs in blood. Mosaic loss of the Y chromosome (mLoY) in blood is the most common post-zygotic mutation in humans. Epidemiological studies have associated mLoY with all-cause mortality and a number of age-associated diseases. However, it is unknown whether there is a causal connection between mLoY and cardiovascular disease. Here, we will employ multiple murine models to assess the impact of mLoY in heart failure, and investigate this relationship at a mechanistic level.