Matrix metalloproteinase-9 is required for adequate angiogenic revascularization of ischemic tissues - Potential role in capillary branching
Matrix metalloproteinase-9 is required for adequate angiogenic revascularization of ischemic tissues - Potential role in capillary branching
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DOI：
10.1161/01.res.0000111527.42357.62
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发表时间：
2004-02-06
影响因子：
20.1
通讯作者：
Galis, ZS
中科院分区：
文献类型：
--
作者：
Johnson, C;Sung, HJ;Galis, ZS
血管生成是各种生理和病理过程的重要组成部分，为治疗调节提供了有吸引力的机会。我们假设基质金属蛋白酶-9基因缺陷（MMP-9（-/-））将损害由组织缺血引发的血管生成，实验诱导小鼠股动脉结扎。为了研究MMP-9的作用，我们进行了一系列的生化和组织学分析，包括酶谱分析、灌注毛细血管的同时检测、MMP-9启动子活性、MMP-9蛋白和MMP-9（-/-）和野生型（WT）小鼠中的巨噬细胞。我们发现，缺血导致WT中毛细血管密度加倍，而MMP-9（-/-）缺血组织中没有变化，这仅在结扎后14天在WT中转化为灌注能力增加（39%）。MMP-9（-/-）区毛细血管呈显著性（P
Angiogenesis, an essential component of a variety of physiological and pathological processes, offers attractive opportunities for therapeutic regulation. We hypothesized that matrix metalloproteinase-9 genetic deficiency (MMP-9(-/-)) will impair angiogenesis triggered by tissue ischemia, induced experimentally by femoral artery ligation in mice. To investigate the role of MMP-9, we performed a series of biochemical and histological analyses, including zymography, simultaneous detection of perfused capillaries, MMP-9 promoter activity, MMP-9 protein, and macrophages in MMP-9(-/-) and wild- type (WT) mice. We found that ischemia resulted in doubling of capillary density in WT and no change in the MMP-9(-/-) ischemic tissues, which translated into increased (39%) perfusion capacity only in the WT at 14 days after ligation. We also confirmed that capillaries in the MMP-9(-/-) presented significantly (P