Post-infarct treatment with an erythropoietin-gelatin hydrogel drug delivery system for cardiac repair

Post-infarct treatment with an erythropoietin-gelatin hydrogel drug delivery system for cardiac repair
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DOI:
10.1093/cvr/cvn154
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发表时间:
2008-09-01
影响因子:
10.8
通讯作者:
Fujiwara, Hisayoshi
Fujiwara, Hisayoshi
中科院分区:
医学1区
文献类型:
--
作者:
Kobayashi, Hiroyuki;Minatoguchi, Shinya;Fujiwara, Hisayoshi

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目的研究促红细胞生成素(EPO)-明胶水凝胶心肌给药系统(DIDS)对心肌梗死(MI)面积、左心室(W)重构和功能的影响。EPO-DDS组心肌梗死后14天和2个月心肌梗死面积缩小,左室重构和功能改善,而心肌梗死后2天无明显改善。分化簇31(CD31)阳性微血管数目和促红细胞生成素受体(EPO-R)、磷酸化Akt(p-Akt)、磷酸化糖原合成酶3β(p-GSK-3β)、磷酸化细胞外信号调节蛋白激酶(p-ERK)、磷酸化信号转导和转录激活剂3(p-STAT3)、血管内皮生长因子(VEGF)和基质金属蛋白酶-1(MMP1)的表达在EPO-DDS组显著增加。结论心肌梗死后EPO-DDS可通过激活促存活信号、抗纤维化、抗纤维化等途径改善左室重构和功能和血管生成,不会引起任何副作用。
Aims We investigated the effect of an erythropoietin (EPO)-gelatin hydrogel drug delivery system (DIDS) applied to the heart on myocardial infarct (MI) size, left ventricular (W) remodelling and function.Methods and results Experiments were performed in a rabbit model of MI. The infarct size was reduced, and LV remodelling and function were improved 14 days and 2 months after MI but not at 2 days after MI in the EPO-DDS group. The number of cluster of differentiation 31 (CD31)-positive microvessels and the expression of erythropoietin receptor (EPO-R), phosphorylated-Akt (p-Akt), phosphorylated glycogen synthase kinase 3 beta (p-GSK-3 beta), phosphorylated extracellular signal-regulated protein kinase (p-ERK), phosphorylated signal transducer and activator of transcription 3 (p-Stat3), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-1 (MMP-1) were significantly increased in the myocardium of the EPO-DDS group.Conclusion Post-MI treatment with an EPO-DDS improves LV remodelling and function by activating pro-survival signalling, antifibrosis, and angiogenesis without causing any side effect.