在这里，研究人员发现，用缺乏Y染色体的骨髓细胞重建的雄性小鼠显示出死亡率增加和与年龄相关的纤维化病变，包括心脏功能降低。缺乏Y染色体的心脏巨噬细胞表现出向更多纤维化表型的极化，并且用转化生长因子β1中和抗体治疗可改善mLOY小鼠的心脏功能障碍。一项前瞻性研究表明，血液中的mLOY与心血管疾病和心力衰竭相关死亡率的风险增加有关。总之，这些结果共同表明，造血功能障碍是导致男性纤维化病变、心脏功能障碍和死亡的原因。
据介绍，Y染色体的造血镶嵌缺失（mLOY）与男性死亡和年龄相关疾病的风险增加有关，但其因果关系和机制尚未确定。
附：英文原文
Title: Hematopoietic loss of Y chromosome leads to cardiac fibrosis and heart failure mortality
Author: Soichi Sano, Keita Horitani, Hayato Ogawa, Jonatan Halvardson, Nicholas W. Chavkin, Ying Wang, Miho Sano, Jonas Mattisson, Atsushi Hata, Marcus Danielsson, Emiri Miura-Yura, Ammar Zaghlool, Megan A. Evans, Tove Fall, Henry N. De Hoyos, Johan Sundstrm, Yoshimitsu Yura, Anupreet Kour, Yohei Arai, Mark C. Thel, Yuka Arai, Josyf C. Mychaleckyj, Karen K. Hirschi, Lars A. Forsberg, Kenneth Walsh
Issue&Volume: 2022-07-15
Abstract: 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.
DOI: abn3100
Source: https://www.science.org/doi/10.1126/science.abn3100