A study appearing in this week's Science reveals new details about how hematopoietic mosaic loss of Y chromosome (mLOY), a condition in which a fraction of hematopoietic cells lose the Y chromosome, contributes to an increased risk of mortality and age-related diseases in men. In the report, a group led by University of Virginia School of Medicine scientists present mouse model data supporting a causal link between hematopoietic mLOY and age-dependent cardiac dysfunction and heart failure in men. Specifically, they show that Y chromosome-deficient cardiac macrophages over-activate a profibrotic signaling network, leading to cardiac fibroblast proliferation and activation, excessive matrix production, and diminished heart function. Meanwhile, treatment with an antibody that neutralizes TGFb1, which is known to promote fibroblast proliferation, ameliorated cardiac dysfunction in mLOY mice. "In view of recent efforts to treat heart failure, idiopathic pulmonary fibrosis, and some cancers with antifibrotic approaches, men with mLOY could represent a patient subpopulation that exhibits a superior response to this class of therapeutic agents," the researchers write.
Link Between Mosaic Loss of Y Chromosome, Heart Failure in Men
Jul 15, 2022