Renin inhibition improves the survival of mesenchymal stromal cells in a mouse model of myocardial infarction.

Renin inhibition improves the survival of mesenchymal stromal cells in a mouse model of myocardial infarction.
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DOI:
10.1007/s12265-014-9575-3
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发表时间:
2014-08
影响因子:
3.4
通讯作者:
Rodriguez-Porcel M
Rodriguez-Porcel M
中科院分区:
医学3区
文献类型:
--
作者:
Franchi F;Ezenekwe A;Wellkamp L;Peterson KM;Lerman A;Rodriguez-Porcel M

文献摘要

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本研究的目的是确定在心肌梗死小鼠模型中,肾素抑制是否能够改善移植干细胞的存活。在FVB/NJ近交系小鼠中诱导心肌梗死(n=23)。将表达报告基因萤火虫荧光素酶的骨髓来源的小鼠间充质基质细胞(mMSCs,3×105)心肌内递送(n=12),并通过生物发光成像非侵入性地监测。一组小鼠(n=6)通过皮下植入的渗透泵接受阿利吉仑(15 mg/kg/天)。在接受阿利吉仑的动物中,mMSCs的存活率显著增加,导致心肌梗死后收缩功能显著改善。组织学分析显示,与对照组相比,接受阿利吉仑的小鼠炎症和胶原沉积显著减少。缺血心肌的肾素抑制能够调节微环境,改善心肌梗死小鼠模型中移植的mMSCs的存活和功效。
The aim of this study was to determine if renin inhibition is able to improve the survival of transplanted stem cells in a mouse model of myocardial infarction. Myocardial infarction was induced in FVB/NJ inbred mice (n=23). Bone marrow-derived mouse mesenchymal stromal cells (mMSCs, 3×105) expressing the reporter gene firefly luciferase were delivered intramyocardially (n=12) and monitored non-invasively by bioluminescence imaging. A group of these mice (n=6) received aliskiren (15 mg/kg/day) via an osmotic pump implanted subcutaneously. The survival of mMSCs was significantly increased in those animals that received aliskiren leading to a significant improvement in systolic function after myocardial infarction. Histological analysis revealed a significant reduction in inflammation and collagen deposition in those mice that received aliskiren compared to controls. Renin inhibition of the ischemic myocardium is able to modulate the microenvironment improving the survival and efficacy of transplanted mMSCs in a mouse model of myocardial infarction.