Endostatin attenuates heart failure via inhibiting reactive oxygen species in myocardial infarction rats

Figure 1. Endostatin overexpression increased survival rate of MI rats (A) Endostatin level was increased in the serum of MI rats. (B) Serum endostatin level was increased in Ad-Endostatin treatment rats. (C) Cardiac endostatin level was increased in Ad-Endostatin treatment rats. (D) Endostatin overexpression increased survival rate of MI rats. The results are expressed as mean ± SEM. n=12. *P<0.05 versus the Sham group; #P<0.05 versus the MI+Ad-GFP group.

Figure 2. Endostatin improved cardiac dysfunction in MI rats The decreases in LV EF and FS, and the increases in LVEDD, LVEDS, LVVD, and LVVS in MI rats were reversed by endostatin overexpression. The results are expressed as mean ± SEM. n=8. *P<0.05 versus the Sham+Ad-GFP group; #P<0.05 versus the MI+Ad-GFP group.

Figure 3. Endostatin improved the impaired cardiac hemodynamics in MI rats The decreases in the maximum of the first differentiation of LV pressure (LV ±dp/dtmax), LVSP, and the increase in LVEDP in MI rats were reversed by endostatin overexpression. The results are expressed as mean ± SEM. n=8. *P<0.05 versus the Sham+Ad-GFP group; #P<0.05 versus the MI+Ad-GFP group.

Figure 4. Endostatin attenuated cardiac fibrosis in MI rats (A) Endostatin overexpression attenuated heart fibrosis of MI rats as revealed by Masson’s staining. (B) The increased expressions of collagen I, collagen III, α-SMA, CTGF, MMP-2 and MMP9 were inhibited by endostatin overexpression. The results are expressed as mean ± SEM. n=8. *P<0.05 versus the Sham+Ad-GFP group; #P<0.05 versus the MI+Ad-GFP group.

Figure 5. Endostatin attenuated cardiac hypertrophy and infarcted area in MI rats (A) Endostatin overexpression attenuated the increase in LV weight, HW, HW/TL, and HW/BW in MI rats. (B) Endostatin overexpression attenuated the increase in cardiomyocyte size in MI rats. (C) Endostatin overexpression attenuated the increase in infarcted area in MI rats. The results are expressed as mean ± SEM. n=8. *P<0.05 versus the Sham+Ad-GFP group; #P<0.05 versus the MI+Ad-GFP group.

Figure 6. Levels of MDA, SOD activity, superoxide anions, and Nox activity MDA, superoxide anions, and Nox activity levels were increased, and SOD activity level was reduced in the heart of MI rats, which was reversed by endostatin overexpression. The results are expressed as mean ± SEM. n=8. *P<0.05 versus the Sham+Ad-GFP group; #P<0.05 versus the MI+Ad-GFP group.

Figure 7. Nox4 overexpression reversed the effects of endostatin overexpression on inhibiting oxidative stresses in the heart of MI rats (A) Nox4 expression was increased in the heart of MI rats treatment with Ad-Nox4. (B) Nox4 overexpression reversed the effects of endostatin on inhibiting the increases in MDA, superoxide anion and Nox activity, and the decrease in SOD activity. The results are expressed as mean ± SEM. n=8. *P<0.05 versus the Ad-GFP (A) or Sham+Ad-GFP (B) group; #P<0.05 versus the MI+Ad-GFP group; &P<0.05 versus the MI+Ad-Endostatin group.

Figure 8. Nox 4 overexpression inhibited endostatin overexpression-induced improvement of cardiac dysfunction in MI rats Nox4 overexpression reversed the endostatin overexpression-induced improvement of LV EF, FS, the increases in LVEDD, LVESD, LVVD, and LVVS in MI rats. The results are expressed as mean ± SEM. n=8. *P<0.05 versus the Sham+Ad-GFP group; #P<0.05 versus the MI+Ad-GFP group; &P<0.05 versus the MI+Ad-Endostatin group.

Figure 9. Nox4 overexpression inhibited endostatin overexpression-induced improvement of cardiac hemodynamics in MI rats Nox4 overexpression reversed the effects of endostatin overexpression on improving the maximum of the first differentiation of LV pressure (LV ±dp/dtmax), LVSP, and LVEDP. The results are expressed as mean ± SEM. n=8. *P<0.05 versus the Sham+Ad-GFP group; #P<0.05 versus the MI+Ad-GFP group; &P<0.05 versus the MI+Ad-Endostatin group.

Figure 10. Nox4 overexpression inhibited endostatin overexpression-induced improvement of cardiac fibrosis in MI rats Nox4 overexpression reversed the effects of endostatin overexpression on reducing the levels of collagen I, collagen III, α- SMA, CTGF, MMP-2, and MMP-9 in the heart of MI rats. The results are expressed as mean ± SEM. n=8. *P<0.05 versus the Sham+Ad-GFP group; #P<0.05 versus the MI+Ad-GFP group; &P<0.05 versus the MI+Ad-Endostatin group.