期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 17, 期 12, 页码 1543-1553出版社
WILEY
DOI: 10.1111/jcmm.12116
关键词
endothelial progenitor cell; matrix metalloproteinase-9; cerebral ischaemia; angiogenesis; neurorepair; stroke
资金
- Miguel Servet programme from the Spanish Ministry of Health [CP09/00265]
- Instituto de Salud Carlos III [PI10/00694]
- European Regional Development Fund
- Spanish Ministry of Health (Instituto de Salud Carlos III, RETICS program, INVICTUS network)
- ERANET-NEURON program from the Ministerio de Economia y Competitividad [2011-1352]
The enhancement of endogenous angiogenesis after stroke will be critical in neurorepair therapies where endothelial progenitor cells (EPCs) might be key players. Our aim was to determine the influence of cerebral ischaemia and the role of matrix metalloproteinase-9 (MMP-9) on the angiogenic function of EPCs. Permanent focal cerebral ischaemia was induced by middle cerebral artery (MCA) occlusion in MMP-9/knockout (MMP-9/KO) and wild-type (WT) mice. EPCs were obtained for cell counting after ischaemia (6 and 24hrs) and in control animals. Matrigel assays and time-lapse imaging were conducted to monitor angiogenic function of WT and MMP9-deficient EPCs or after treatment with MMP-9 inhibitors. Focal cerebral ischaemia increased the number of early EPCs, while MMP-9 deficiency decreased their number in non-ischaemic mice and delayed their release after ischaemia. Late outgrowth endothelial cells (OECs) from ischaemic mice shaped more vessel structures than controls, while MMP-9 deficiency reduced the angiogenic abilities of OECs to form vascular networks, in vitro. Treatment with the MMP inhibitor GM6001 and the specific MMP-9 inhibitor I also decreased the number of vessel structures shaped by both human and mouse WT OECs, while exogenous MMP-9 could not revert the impaired angiogenic function in MMP-9/KO OECs. Finally, time-lapse imaging showed that the extension of vascular networks was influenced by cerebral ischaemia and MMP-9 deficiency early during the vascular network formation followed by a dynamic vessel remodelling. We conclude that focal cerebral ischaemia triggers the angiogenic responses of EPCs, while MMP-9 plays a key role in the formation of vascular networks by EPCs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据