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GW24-e2387 Cyclin-A2 promotes cardiac self-repair via the recruitment of cardiac stem cells after myocardium infarction
  1. Zhao Aichao,
  2. Aichao Zhao,
  3. Xiang Ma,
  4. Yongzhao Yao,
  5. Wen Cao,
  6. Fen LiuBangdang,
  7. Bangdang Chen,
  8. Xiangma
  1. Department of Coronary Heart Disease

Abstract

Objectives To determine whether or not exogenous Cyclin-A2 promotes cardiac self-repair and restart cardiomyocytes cycle in vivo after MI.

Methods Sixty mice were randomly divided into two groups; MI + saline (n = 30) and MI + rAAV9-CMV-Cyclin-A2 (n = 30). 2×1011 genome copies in 200ul saline were delivered into the mice myocardium through the caudal vein one week before MI. The control group was injected with saline at same volume and time. Post MI observation was one week and three weeks respectively. Echocardiography was performed to measure LVEDD, LVESD, and EF. Western Blot and immunohistochemical analysis were used to detect the expression and location of Cyclin-A2. DNA synthesis and mitosis were analysed by PCNA and phosphohistone-H3 respectively. C-Kit and connexin 43, which were defined as cardiac stem cells markers, were also measured.

Results Western Blot showed that expression of Cyclin-A2 started at two weeks and peaked at four weeks after injection. Expression of Cyclin-A2 in two groups had a significant statistical difference with p < 0.01. PCNA was specific in S phase and exhibited higher expression in Cyclin-A2 treated group than control group (0.75 ± 0.03 vs 0.43 ± 0.02, p = 0.036). However, mitosis specific protein H3P had no statistical difference between the two groups (p > 0.05). C-Kit and connexin 43 showed an increase in Cyclin-A2 treated group, but no change in control group (p < 0.05). Immunohistochemistry showed that Cyclin-A2 after transfection was located in cytoplasm but not in nucleus. A decreased level of collagen I and III was observed in Cyclin-A2 treated group than control group (p = 0.029) by Masson Triple Stain. There was significant difference in LVEDD, LVESD, and EF between the two groups (0.31 ± 0.02 cm vs 0.44 ± 0.01 cm, 0.21 ± 0.02 cm vs 0.34 ± 0.01 cm and 55 ± 2.3% vs 40 ± 1.7%).

Conclusions Cyclin-A2 promotes cardiac self-repair via the recruitment of cardiac stem cells and restart cardiomyocytes cycle after myocardial infarction.

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