Spontaneous bleeding and increased vascular permeability in PAI-1^−/− hearts. Prussian blue staining of 12- and 48-week WT (A-B) and PAI-1^−/− (C-D) hearts revealed hemosiderin deposition in 12-week PAI-1^−/− hearts (C, ↑), indicating bleeding before fibrosis formation. Hemosiderin deposition was overt in 48-week PAI-1^−/− hearts (D). An in vivo vascular permeability assay revealed increased cardiac vascular leakage in 12-week PAI-1^−/− hearts (E). The plasma levels of EB were the same between WT and PAI-1^−/− mice (F). Gross photograph of PAI-1^−/− hearts at 48 weeks is shown (G), where hemorrhage spots are observable macroscopically (↑). n ≥ 5 for each age group; *P < .05.