Figure 5: BIO rescues an animal model of experimental heart failure by inducing cardiomyocyte proliferation. n = 20/group.

(A) Treatment of 72 hpf Tg(cmlc2:GFP) transgenic zebrafish larvae with 2.5 μM aristolochic acid (AA) for 3 hours induces cardiomyocyte death, which can be visualized as reduced heart size in treated larvae at 168 hpf. Treatment with 5 μM BIO, but not 20 mM LiCl increased ventricular size. *P < 0.05, t-test. (B) BIO treatment completely recovered survival rate in AA-treated animals. LiCl treatment increased survival rate, but not to the same degree as BIO treated animals. *p < 0.05, t-test. (C) Micrographs of the cardiac drug-treated larvae showed that BIO increased the number of proliferating cardiomyocytes in AA-treated animals, as detected by counting BrdU-immunostained cells in the GFP-positive cardiac region (cardiomyocytes = green; BrdU positive cells = red). *p < 0.05, t-test. Scale bar = 100 μm.