Department of Cardiology, The Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine.
Department of Gerontology, The Second Affiliated Hospital, Zhejiang University School of Medicine.
Circ J. 2018 Aug 24;82(9):2332-2341. doi: 10.1253/circj.CJ-17-1251. Epub 2018 Jul 10.
In a previous study, a low level of miR-126-3p in endothelial progenitor cells (EPCs) was linked to the outcome of ischemic cardiomyopathy (ICM) patients. However, it remains unclear whether transplantation with miR-126-3p-overexpressing EPCs (MO-EPCs) can improve the cardiac function of ICM animal models.
miR-126-3p overexpression by lentiviral vector significantly increased migration and tube-like structures of EPCs from ICM patients. MO-EPCs or non-modified EPCs (NM-EPCs) were transplanted into nude rats with ICM induced by coronary artery ligation. MO-EPC transplantation increased capillary density and EPC survival rate in myocardial tissues of nude rats. Cytokines were also assessed by antibody array and real-time RT-PCR. G-CSF, VEGF-A, IL-3, IL-10, IGF-1, angiogenin, HGF, TIMP-1 and TIMP-2 were upregulated, and IL-8, MCP-1, MCP-2, TNF-α, TNF-β and MIP-1β were downregulated after miR-126-3p overexpression in EPCs. The same results were obtained in infarction tissues of nude rats after MO-EPC transplantation. Eight weeks after MO-EPC transplantation, left ventricular function improved significantly with clearly decreased infarction size, increased anterior wall thickness, and inhibition of inflammation compared with the results for NM-EPC transplantation. However, MO-EPC transplantation showed no increase in survival time of nude rats with ICM during 8 weeks of observation.
miR-126-3p can restore the biology of EPCs from ICM patients. Moreover, MO-EPC transplantation improves cardiac function effectively, representing a promising future treatment for ICM.
在之前的一项研究中，内皮祖细胞（EPCs）中 miR-126-3p 的低水平与缺血性心肌病（ICM）患者的预后相关。然而，用 miR-126-3p 过表达的 EPCs（MO-EPCs）移植是否能改善 ICM 动物模型的心脏功能仍不清楚。
慢病毒载体的 miR-126-3p 过表达显著增加了来自 ICM 患者的 EPCs 的迁移和管状结构。MO-EPCs 或非修饰的 EPCs（NM-EPCs）被移植到冠状动脉结扎诱导的 ICM 裸鼠中。MO-EPC 移植增加了裸鼠心肌组织中的毛细血管密度和 EPC 存活率。通过抗体阵列和实时 RT-PCR 评估细胞因子。G-CSF、VEGF-A、IL-3、IL-10、IGF-1、血管生成素、HGF、TIMP-1 和 TIMP-2 上调，而 IL-8、MCP-1、MCP-2、TNF-α、TNF-β 和 MIP-1β 在 EPCs 中过表达后下调。MO-EPC 移植后裸鼠梗塞组织也得到了同样的结果。MO-EPC 移植 8 周后，与 NM-EPC 移植相比，左心室功能明显改善，梗塞面积明显减小，前壁厚度增加，炎症抑制。然而，MO-EPC 移植并没有增加 8 周观察期内 ICM 裸鼠的存活时间。
miR-126-3p 可以恢复来自 ICM 患者的 EPCs 的生物学特性。此外，MO-EPC 移植有效地改善了心脏功能，代表了一种有前途的 ICM 治疗方法。
