Ang-1 attenuates myocardial/endothelial apoptosis, and reduces cardiac fibrosis and hypertrophy in db/db mouse.

<p><i>A.</i> TUNEL-stained heart sections from sham control db/db mouse, db/db mouse treated with Ad-β-gal or Ad-Ang-1 at 24 hours and 14 days of MI. Myocardial and endothelial apoptotic cells in the infarcted area of the ischemic hearts were identified by TUNEL staining (green) and TUNEL/vWF (red) positive staining, and total nuclei by DAPI counterstaining (blue). <i>B and C.</i> Quantitative analysis of apoptotic cells in sham control db/db mouse and infarcted area of db/db mouse treated with Ad-β-gal or Ad-Ang-1 at 24 hours and 14 days after ischemia. TUNEL or TUNEL/vWF positive cells are expressed as the total number of per mm². Apoptotic cells were significantly decreased in Ad-Ang-1 compared to Ad-β-gal mice. All data represent mean ± SD (n = 4 mice); *p<0.05. <i>D.</i> Representative images and quantitative analysis of apoptotic cells in the remote area of infarction of db/db mouse at 24 hours after ischemia. Apoptotic cells were significantly decreased in Ad-Ang-1 treated db/db mouse hearts (n = 5) compared to Ad-β-gal treated db/db mice (n = 7). All data represent mean ± SD; sham control n = 5, *p<0.05. <i>E.</i> Representative images of TUNEL and SMA-stained heart sections from sham control db/db mouse, db/db mouse treated with Ad-β-gal or Ad-Ang-1 at 24 hours and 14 days of MI. Myocardial and SMCs apoptotic cells in the infarcted area of the ischemic hearts were identified by TUNEL (green) and SMA (red) positive staining, and total nuclei by DAPI counterstaining (blue). <i>F.</i> Representative images of cardiac fibrosis formation and quantitative analysis of cardiac fibrosis area in db/db mice treated with Ad-β-gal or Ad-Ang-1 stained by Masson’s trichrome. Ad-Ang-1 significantly attenuated area of cardiac fibrosis in db/db mice compared to Ad-β-gal mice. All data represent mean ± SD (n = 5 mice); *p<0.05. <i>G.</i> Heart weight/body weight (HW/BW) ratio in db/db and Ad-Ang-1-treated db/db mouse hearts at 14 days after MI. Treatment with Ad-Ang-1 significantly attenuated cardiac hypertrophy in db/db mouse hearts (n = 5) compared to Ad-β-gal mice (n = 4). All data represent mean ± SD; *p<0.05.