论文
论文标题：Hematopoietic loss of Y chromosome leads to cardiac fibrosis and heart failure mortality
作者：Soichi Sano, Keita Horitani, Hayato Ogawa, Jonatan Halvardson , Nicholas W. Chavkin, Ying Wang, et al.
期刊：Science
发表时间：2022/07/14
数字识别码：10.1126/science.abn3100
摘要：Hematopoietic mosaic loss of Y chromosome (mLOY) is associated with increased risk of mortality and age-related diseases in men, but the causal and mechanistic relationships have yet to be established. Here, we show that male mice reconstituted with bone marrow cells lacking the Y chromosome display increased mortality and age-related profibrotic pathologies including reduced cardiac function. Cardiac macrophages lacking the Y chromosome exhibited polarization toward a more fibrotic phenotype, and treatment with a transforming growth factor β1–neutralizing antibody ameliorated cardiac dysfunction in mLOY mice. A prospective study revealed that mLOY in blood is associated with an increased risk for cardiovascular disease and heart failure–associated mortality. Together, these results indicate that hematopoietic mLOY causally contributes to fibrosis, cardiac dysfunction, and mortality in men.
所属学科：
遗传学
(领研网导读 J.T.) 造血细胞中Y染色体的镶嵌性缺失（mLOY）会增加男性死亡和年龄相关疾病的风险，但其中机制尚不清楚。本研究发现，骨髓细胞中缺乏 Y 染色体的雄性小鼠死亡率增高且有与年龄相关的纤维化病变，如心脏功能降低。缺乏 Y 染色体的心脏巨噬细胞倾向于表现出纤维化表型。利用转化生长因子 β1 中和抗体治疗可改善 mLOY 小鼠的心脏功能障碍。前瞻性研究表明，血液中的 mLOY 与心血管疾病和心力衰竭风险升高相关。
