| Title: | Hematopoietic loss of Y chromosome leads to cardiac fibrosis and heart failure mortality |
| Journal: | Science |
| Published: | 14 Jul 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/35857592/ |
| DOI: | https://doi.org/10.1126/science.abn3100 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9437978 |
Publication 10357
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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.</p>
25 Authors
- 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 Sundström
- Yoshimitsu Yura
- Anupreet Kour
- Yohei Arai
- Mark C Thel
- Yuka Arai
- Josyf C Mychaleckyj
- Karen K Hirschi
- Lars A Forsberg
- Kenneth Walsh
1 Application
| Application ID | Title |
|---|---|
| 61272 | New investigations of associations between mosaic loss of chromosome Y (LOY) and other somatic mutations in blood cells with increased risk for human disease outcomes |
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