Interdisciplinary Stem Cell Institute, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida, USA.
Clin Transl Sci. 2011 Jun;4(3):168-74. doi: 10.1111/j.1752-8062.2011.00278.x.
Erythropoietin (EPO) has the potential to improve ischemic tissue by mobilizing endothelial progenitor cells and enhancing neovascularization. We hypothesized that combining EPO with human chorionic gonadotrophin (hCG) would improve post-myocardial infarction (MI) effects synergistically.
After MI, five to seven animals were randomly assigned to each of the following treatments: control; hCG; EPO; hCG + EPO, and prolactin (PRL) + EPO. Follow-up echocardiograms were performed to assess cardiac structure and function. Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay and western blot analysis for apoptosis-related proteins, and cell proliferation by immunostaining for Ki67 and c-kit cells.
The MI-mediated increased chamber systolic dimension (p < 0.05 in controls) was attenuated by hCG, EPO, and hCG + EPO (p < 0.05 vs. control) but not PRL + EPO. Similarly all treatment groups, except PRL + EPO, reduced MI-induced increases (p < 0.05 vs. control) in ejection fraction (EF). The functional improvement in the EPO-treated groups was accompanied by increased capillary density. Apoptosis was markedly reduced in all treated groups. Significantly more cardiac c-kit(+) cells were found in the hCG + EPO group.
Our findings revealed that EPO, hCG, or their combination ameliorate cardiac remodeling post-MI. Whereas EPO stimulates neovascularization only and hCG + EPO stimulates c-kit+ cell proliferation. These data suggest that combining mobilizing and proliferative agents adds to the durability and sustainability of cytokine-based therapies for remodeling post-MI.
促红细胞生成素（EPO）具有通过动员内皮祖细胞和增强新生血管化来改善缺血组织的潜力。我们假设将 EPO 与人绒毛膜促性腺激素（hCG）结合使用会协同改善心肌梗死后（MI）的效果。
MI 后，将五到七只动物随机分配到以下治疗组中的每一组：对照组；hCG；EPO；hCG+EPO 和催乳素（PRL）+EPO。进行后续超声心动图检查以评估心脏结构和功能。通过末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）测定和凋亡相关蛋白的 Western blot 分析来确定细胞凋亡，并用 Ki67 和 c-kit 细胞的免疫染色来确定细胞增殖。
MI 介导的腔室收缩尺寸增加（对照组中 p < 0.05）被 hCG、EPO 和 hCG+EPO 减弱（与对照组相比 p < 0.05），但 PRL+EPO 组没有减弱。同样，除了 PRL+EPO 组外，所有治疗组均降低了 MI 诱导的射血分数（EF）增加（与对照组相比 p < 0.05）。EPO 治疗组的功能改善伴随着毛细血管密度的增加。所有治疗组的细胞凋亡均明显减少。在 hCG+EPO 组中发现更多的心脏 c-kit+细胞。
我们的研究结果表明，EPO、hCG 或它们的组合可改善 MI 后心脏重塑。EPO 仅刺激血管新生，而 hCG+EPO 刺激 c-kit+细胞增殖。这些数据表明，结合动员和增殖剂可增强基于细胞因子的 MI 后重塑治疗的耐久性和可持续性。
