Conditional Expression of the Type 2 Angiotensin II Receptor in Mesenchymal Stem Cells Inhibits Neointimal Formation After Arterial Injury
Conditional Expression of the Type 2 Angiotensin II Receptor in Mesenchymal Stem Cells Inhibits Neointimal Formation After Arterial Injury
复制标题
间充质干细胞中 2 型血管紧张素 II 受体的条件表达可抑制动脉损伤后新内膜的形成。
DOI：
10.1007/s12265-014-9576-2
复制
发表时间：
2014-10-01
影响因子：
3.4
通讯作者：
Jing, Tao
中科院分区：
文献类型：
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作者：
Feng, Jian;Liu, Jian-Ping;Jing, Tao
经皮冠状动脉介入治疗(PCI)是治疗阻塞性冠状动脉疾病的有效方法。然而，该手术的成功受到新生内膜重塑和形成的限制。在本研究中，我们利用四环素调控系统使大鼠骨髓间充质干细胞(MSCs)表达2型血管紧张素II受体(AT2R)，该系统可以严格调控AT2R的表达。我们测试了改良的MSCs减少动脉损伤后新生内膜形成的能力。我们对大鼠进行了球囊损伤，逆转录聚合酶链式反应(RT-PCR)显示正常大鼠动脉中没有明显的AT2R表达。球囊损伤后28d，AT2R低表达。有趣的是，单独的MSCs不能减少球囊损伤后新生内膜的增殖；在修饰的MSCs移植后，多西环素治疗显著上调新内膜AT2R的表达，抑制骨桥蛋白mRNA的表达，以及新内膜的形成。综上所述，这些结果表明，移植有条件表达AT2R的MSCs可以有效地抑制球囊损伤后的新生内膜增生。因此，具有多西环素调控的基因诱导系统的骨髓间充质干细胞可能对经皮冠状动脉介入术后的动脉损伤有一定的治疗作用。
Percutaneous coronary interventions (PCIs) are an effective treatment for obstructive coronary artery diseases. However, the procedure's success is limited by remodeling and formation of neointima. In the present study, we engineered rat mesenchymal stem cells (MSCs) to express type 2 angiotensin II receptor (AT2R) using a tetracycline-regulated system that can strictly regulate AT2R expression. We tested the ability of the modified MSCs to reduce neointima formation following arterial injury. We subjected rats to balloon injury, and reverse transcriptase polymerase chain reaction (RT-PCR) indicated no significant AT2R expression in normal rat arteries. Low expression of AT2R was observed at 28 days after balloon-induced injury. Interestingly, MSCs alone were unable to reduce neointimal hyperplasia after balloon-induced injury; after transplantation of modified MSCs, doxycycline treatment significantly upregulated neointimal AT2R expression and inhibited osteopontin mRNA expression, as well as neointimal formation. Taken together, these results suggest that transplantation of MSCs conditionally expressing AT2R could effectively suppress neointimal hyperplasia following balloon-induced injury. Therefore, MSCs with a doxycycline-controlled gene induction system may be useful for the management of arterial injury after PCI.