Localized Delivery of shRNA against PHD2 Protects the Heart from Acute Myocardial Infarction through Ultrasound-Targeted Cationic Microbubble Destruction.
文献类型：期刊论文
| 作者 | Yan, Fei; Zhang, Li; Sun, Zhenxing; Ren, Pingping; You, Manjie; Zhang, Jing; Fang, Lingyun; Chen, Yihan; Zheng, Hairong |
| 刊名 | THERANOSTICS
 |
| 出版日期 | 2017 |
| 文献子类 | 期刊论文 |
| 英文摘要 | Hypoxia-inducible factor 1 alpha (HIF-1 alpha) plays a critical protective role in ischemic heart disease. Under normoxic conditions, HIF-1 alpha was degraded by oxygen-dependent prolyl hydroxylase-2 (PHD2). Gene therapy has become a promising strategy to inhibit the degradation of HIF-1 alpha and to improve cardiac function after ischemic injury. However, conventional gene delivery systems are difficult to achieve a targeted and localized gene delivery into the ischemic myocardia. Here, we report the localized myocardial delivery of shRNA against PHD2 through ultrasound-targeted microbubble destruction (UTMD) for protection the heart from acute myocardial infarction. In this study, a novel cationic microbubble was fabricated by using of the thin-film hydration and sonication method. The resulting microbubbles had a 28.2 +/- 2.21 mV surface zeta potential and could greatly improve DNA binding performance, achieving 17.81 +/- 1.46 mu g of DNA loading capacity per 5 x 10(8) microbubbles. Combined with these cationic microbubbles, UTMD-mediated gene delivery was evaluated and the gene transfection efficiency was optimized in the H9C2 cardiac cells. Knockdown of PHD2 gene was successfully realized by UTMD-mediated shPHD2 transfection, resulting in HIF-1 alpha-dependent protective effects on H9C2 cells through increasing the expression of HIF-1 alpha, VEGF and bFGF. We further employed UTMD-mediated shPHD2 transfection into the localized ischemic myocardia in a rat ischemia model, demonstrating significantly reduced infarct size and greatly improved the heart function. The silencing of PHD2 and the up-regulation of its downstream genes in the treated myocardia were confirmed. Histological analysis further revealed numbers of HIF-1 alpha- and VEGF-, and CD31-positive cells/mm(2) in the shPHD2-treated group were significantly greater than those in the sham or control vector groups (P < 0.05). In conclusion, our study provides a promising strategy to realize ultrasound-mediated localized myocardial shRNA delivery to protect the heart from acute myocardial infarction via cationic microbubbles. |
| URL标识 | 查看原文 |
| 语种 | 英语 |
| 源URL | [http://ir.siat.ac.cn:8080/handle/172644/12057]  |
| 专题 | 深圳先进技术研究院_医工所 |
| 作者单位 | THERANOSTICS |
| 推荐引用方式 GB/T 7714 | Yan, Fei,Zhang, Li,Sun, Zhenxing,et al. Localized Delivery of shRNA against PHD2 Protects the Heart from Acute Myocardial Infarction through Ultrasound-Targeted Cationic Microbubble Destruction.[J]. THERANOSTICS,2017. |
| APA | Yan, Fei.,Zhang, Li.,Sun, Zhenxing.,Ren, Pingping.,You, Manjie.,...&Zheng, Hairong.(2017).Localized Delivery of shRNA against PHD2 Protects the Heart from Acute Myocardial Infarction through Ultrasound-Targeted Cationic Microbubble Destruction..THERANOSTICS. |
| MLA | Yan, Fei,et al."Localized Delivery of shRNA against PHD2 Protects the Heart from Acute Myocardial Infarction through Ultrasound-Targeted Cationic Microbubble Destruction.".THERANOSTICS (2017). |
入库方式： OAI收割
来源：深圳先进技术研究院
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