Matrix metalloproteinase-9 modulation by resident arterial cells is responsible for injury-induced accelerated atherosclerotic plaque development in apolipoprotein E-deficient mice
Matrix metalloproteinase-9 modulation by resident arterial cells is responsible for injury-induced accelerated atherosclerotic plaque development in apolipoprotein E-deficient mice
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DOI：
10.1161/01.atv.0000161275.82687.f6
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发表时间：
2005-05-01
影响因子：
8.7
通讯作者：
Parks, WC
中科院分区：
文献类型：
--
作者：
Choi, ET;Collins, ET;Parks, WC
目的：尽管基质金属蛋白酶-9（MMP-9）与动脉粥样硬化斑块的不稳定性有关，但其在斑块发生和发展中的确切作用仍不清楚。我们用载脂蛋白E（apoE）缺陷的（apoE（-/-））MMP-9缺陷型（MMP-9（-/-））小鼠，以确定在加速的动脉粥样硬化斑块形成期间负责斑块组成的MMP-9的机制和主要细胞来源。与apoE（-/-）MMP-9（+/+）小鼠相比，apoE（-/-）MMP-9（-/-）小鼠的内膜斑块长度和体积显著减少。斑块体积的减少与常驻细胞和骨髓源性细胞的斑块内细胞数量显著减少相关。为了确定MMP-9在斑块形成中的细胞来源，用apoE（-/-）MMP-9（+/+）和apoE（-/-）MMP-9（-/-）小鼠进行全身照射后的骨髓移植，这表明只有来自常驻动脉细胞的MMP-9是斑块发展所必需的。9来源于常驻动脉细胞，并且是apoE（-/-）小鼠中早期动脉粥样硬化斑块发展和细胞积累所需的。
Objective - Although matrix metalloproteinase-9 (MMP-9) has been implicated in atherosclerotic plaque instability, the exact role it plays in the plaque development and progression remains largely unknown. We generated apolipoprotein E ( apoE) - deficient ( apoE(-/-)) MMP-9 - deficient (MMP-9(-/-)) mice to determine the mechanisms and the main cell source of MMP-9 responsible for the plaque composition during accelerated atherosclerotic plaque formation.Methods and Results - Three weeks after temporary carotid artery ligation revealed that while on a Western-type diet, apoE(-/-) MMP-9(-/-) mice had a significant reduction in intimal plaque length and volume compared with apoE(-/-) MMP-9(+/+) mice. The reduction in plaque volume correlated with a significantly lower number of intraplaque cells of resident cells and bone marrow - derived cells. To determine the cellular origin of MMP-9 in plaque development, bone marrow transplantation after total-body irradiation was performed with apoE(-/-) MMP-9(+/+) and apoE(-/-) MMP-9(-/-) mice, which showed that only MMP-9 derived from resident arterial cells is required for plaque development.Conclusions - MMP-9 is derived from resident arterial cells and is required for early atherosclerotic plaque development and cellular accumulation in apoE(-/-) mice.