Chronic administration of isoproterenol causes excessive myocyte death and cardiac fibrosis in Stat3cKO hearts. A, Chronic ISO stimulation induces excessive cardiomyocyte death in Stat3cKO hearts. Upper panel shows representative images of Evans blue (in red) uptake in control and Stat3cKO hearts with or without 7-day ISO perfusion (400x). WGA, in green; DAPI, in blue. Lower panel shows the quantitation of Evans blue positive myocytes in control and Stat3cKO hearts (N = 5/each group). B, Upper panel shows Sirius red and fast green staining to demonstrate the collagen deposition in control and Stat3cKO hearts with or without 7-day ISO perfusion (N = 5/each group). Lower panel shows the quantification of collagen contents, *P<0.05, **P<0.01. C, Representative results of Western blots show the reduced levels of Bcl-xl and the increased levels of pSmad2 in Stat3cKO hearts after 4 days of continuous ISO stimulation when compared with controls. D–E, Representative images of IHC staining of pY-STAT3 in control and Stat3cKO hearts after 7-day ISO perfusion. Activated STAT3 are found enhanced in myofibroblast cells in Stat3cKO hearts.