Fig. 1

Mechanism behind the association of mLOY with cardiac fibrosis through cardiac localization of hematogenic mLOY macrophages. Although hematopoietic stem cells originally begin in the embryonic yolk sac, then the liver and dorsal aorta, by adult life, hematopoiesis lies in the bone marrow. Thus, mosaic loss of Y-chromosome in peripheral leukocytes originate in marrow myeoloid progenetors. The resultant mLOY leukocytes are then distributed throughout the body, including in to the myocardium and atrial-ventricular node, where their enrichment of TGFb1 expression and suppression of IL-1b expression promotes pro-fibrotic response to stress resulting in heart failure and arrhythmia. AVN, Atrial-ventricle node; CFB, Central fibrous body; POI, Plane of insulation