Histochemical characterization of interstitial cardiac fibrosis in hearts of PAI-1^−/− mice. H&E staining of WT hearts at (A) 12 and (B) 48 weeks, and PAI-1^−/− hearts at (C) 12 and (D) 48 weeks. At 48 weeks, replacement of cardiomyocytes by connective tissue was observed in PAI-1^−/− hearts (black arrow). Masson trichrome staining of WT hearts at (E) 12 and (F) 48 weeks, and PAI-1^−/− hearts at (G) 12 and (H) 48 weeks revealed extensive interstitial collagen deposition (white arrow, blue staining) in 48-week PAI-1^−/− hearts. Although 12-, 24-, 36-, and 48-week hearts were examined, only 12- and 48-week hearts are shown in this figure. Global view of 48-week PAI-1^−/− hearts with H&E staining (I) and Masson trichrome staining (J) revealed that fibrosis formation (black arrow) was rather pervasive throughout the entire heart. (K) Quantification of collagen by Masson trichrome staining of hearts. Data points represent individual hearts, and bars are group means. n ≥ 4 for each age group; *P < .05.