PAI-1 deficiency causes spontaneous cardiac fibrosis formation. (A-F) Macroscopic views of hearts from WT and PAI-1^−/− mice. (A-C) WT hearts at 24, 36, and 48 weeks, respectively. None of the WT hearts at any time point examined developed fibrosis. (D-F) PAI-1^−/− hearts at 24, 36, and 48 weeks, respectively. PAI-1^−/− mice at 36 and 48 weeks developed obvious cardiac fibrosis. The fibrotic patches (red arrows) show a loss of normal architecture, paucity of stromal cells, and replacement of essential parenchymal structures by dense, pale, and increasingly rigid tissue. (G) Cardiac fibrosis formation caused an increase in the heart–body weight ratio (mg/g) in PAI-1^−/− mice with aging, compared with WT mice. (H) PAI-1 antigen levels in plasma. n ≥ 8 for each age group; *P < .05.