Fujita Masanori, Otani Hajime, Iwasaki Masayoshi, Yoshioka Kei, Shimazu Takayuki, Shiojima Ichiro, Tabata Yasuhiko
Department of Medicine II, Kansai Medical University, Moriguchi City, Japan.
Department of Biomaterials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto City, Japan.
Regen Ther. 2016 Jul 16;5:9-16. doi: 10.1016/j.reth.2016.04.002. eCollection 2016 Dec.
We investigated whether attachment of gelatin hydrogel microsphere (GHM) sheet impregnated with antagomir-92a on the infarcted heart promotes angiogenesis and cardiomyogenesis, and improves cardiac function after myocardial infarction (MI) in rats.
GHM sheet impregnated with antagomir-92a, its scramble sequence antagomir-control sheet or the sheet alone was attached on the area at risk of MI after the left anterior descending coronary artery ligation. Bromodeoxyuridine (BrdU) was included in the sheet to trace proliferating cells.
The antagomir-92a sheet significantly increased capillary density in the infarct border zone 14 days after MI compared to the antagomir-control sheet or the sheet alone, associated with an increase in endothelial cells incorporated with BrdU. The antagomir-92a sheet significantly increased cardiac stem cells incorporated with BrdU 3 days after MI in the infarct border zone. This was associated with an increase in cardiomyocytes incorporated with BrdU 14 days after MI. Scar area was significantly reduced by the antagomir-92a sheet compared to the antagomir-control sheet or the sheet alone (12.8 ± 1.3 vs 25.2 ± 2.2, 24.0 ± 1.7% LV area, respectively) 14 days after MI. LV dilatation was inhibited, and LV wall motion was improved 14 days after MI in rats with the antagomir-92a sheet compared to the antagomir-control sheet or the sheet alone.
These results suggest that attachment of the GHM sheet impregnated with antagomir-92a on the area at risk of MI enhances angiogenesis, promotes cardiomyogenesis, and ameliorates LV function.
我们研究了在梗死心脏上附着浸渍有抗 miR-92a 的明胶水凝胶微球（GHM）片是否能促进血管生成和心肌生成，并改善大鼠心肌梗死后的心脏功能。
在左冠状动脉前降支结扎后，将浸渍有抗 miR-92a 的 GHM 片、其乱序序列抗 miR 对照片或单纯该片附着于心肌梗死危险区域。该片中包含溴脱氧尿苷（BrdU）以追踪增殖细胞。
与抗 miR 对照片或单纯该片相比，抗 miR-92a 片在心肌梗死后 14 天显著增加了梗死边缘区的毛细血管密度，这与掺入 BrdU 的内皮细胞增加有关。抗 miR-92a 片在心肌梗死后 3 天显著增加了梗死边缘区掺入 BrdU 的心脏干细胞。这与心肌梗死后 14 天掺入 BrdU 的心肌细胞增加有关。与抗 miR 对照片或单纯该片相比，抗 miR-92a 片在心肌梗死后 14 天显著减少了瘢痕面积（分别为左心室面积的 12.8±1.3%与 25.2±2.2%、24.0±1.7%）。与抗 miR 对照片或单纯该片相比，在植入抗 miR-92a 片的大鼠中，心肌梗死后 14 天左心室扩张受到抑制，左心室壁运动得到改善。
这些结果表明，在心肌梗死危险区域附着浸渍有抗 miR-92a 的 GHM 片可增强血管生成，促进心肌生成，并改善左心室功能。
