Figure 2.

3 MA reversed cardiac remodeling and attenuated BNIP3 expression in heart failure. (a) M-mode images of the sham placebo and the 3 MA-treated groups at the onset of heart failure and 1 month after treatment. (b and c) There was a significant decrease in left ventricular end diastolic and end systolic volume, as well as a significant increase in ejection fraction 1 month after 3 MA treatment compared with placebo, ^#P<0.05 versus HF+3 MA and HF+Placebo, ^*P<0.05 versus HF+Placebo. (d and e) Hemodynamically, there was a trend in improved left ventricular efficiency in the 3 MA-treated group; however, there was a significant increase in left ventricular contractility and efficiency in response to β-adrenergic stimulation with dobutamine, ^*P<0.05 versus HF+placebo. (f) Western blot analysis of LV tissue lysate from control, HF+Placebo and HF+3 MA groups. BNIP3 and MurF-1 expression were significantly increased in HF, ^#P<0.05 versus CTL. 3 MA treatment significantly decreased the expression of FOXO3a effectors BNIP3 and MurF-1, ^*P<0.05 versus HF+Placebo. (g) Ultrustructurally, 3MA attenuated the presence of autophagolysosomes and restored mitochondrial cristae; whereas, the placebo group had severely defragmented mitochondria with the presence of autophagolysosomes (white arrows), images × 12 000 magnified. (h) 3 MA significantly improved mitochondrial area, ^*P<0.05 versus HF+Placebo, ^#P<0.05 versus HF+Placebo and HF+3 MA. (i) showing the correlation between mitochondrial area and BNIP3 expression. 3 MA decreased BNIP3 expression in heart failure and significantly improved the area per unit mitochondrion, ^*P<0.05 versus HF+Placebo