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Sano, Soichi; Horitani, Keita; Ogawa, Hayato; Halvardson, Jonatan; Chavkin, Nicholas W; Wang, Ying; Sano, Miho; Mattisson, Jonas; Hata, Atsushi; Danielsson, Marcus; Miura-Yura, Emiri; Zaghlool, Ammar; Evans, Megan A; Fall, Tove; De Hoyos, Henry N; Sundström, Johan; Yura, Yoshimitsu; Kour, Anupreet; Arai, Yohei; Thel, Mark C; Arai, Yuka; Mychaleckyj, Josyf C; Hirschi, Karen K; Forsberg, Lars A; Walsh, Kenneth
Science (American Association for the Advancement of Science), 07/2022, Letnik: 377, Številka: 6603Journal Article
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.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Vir: Osebne bibliografije
in: SICRIS
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