High glucose alters matrix metalloproteinase expression in two key vascular cells: potential impact on atherosclerosis in diabetes
High glucose alters matrix metalloproteinase expression in two key vascular cells: potential impact on atherosclerosis in diabetes
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DOI：
10.1016/s0021-9150(03)00140-0
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发表时间：
2003-06-01
期刊：
影响因子：
5.3
通讯作者：
Yue, DK
中科院分区：
文献类型：
--
作者：
Death, AK;Fisher, EJ;Yue, DK
糖尿病是动脉粥样硬化的主要危险因素。高血压是一个潜在的影响因素;然而，介导血管并发症的机制尚未完全了解。在本研究中，我们提供的证据表明，葡萄糖升高诱导不协调的基质金属蛋白酶（MMP）表达的两个关键血管细胞，内皮细胞和巨噬细胞。我们的研究结果清楚地表明，高糖（25 mM）诱导内皮细胞表达和活性的胶原酶，MMP-1和明胶酶，MMP-2，而基质溶解素，MMP-3的表达减少（P < 0.05）。同样，我们的结果表明，高糖（25 mM）诱导MMP-9从单核细胞衍生的巨噬细胞的表达和活性（P < 0.05）。高糖培养不影响基质金属蛋白酶抑制剂（TIMP-1）的表达。我们的研究结果首次表明，高糖暴露诱导血管细胞MMP/TIMP系统的不协调调节。高糖暴露诱导的MMP-1、MMP-2和MMP-9活性增加可促进基质降解，从而加速动脉粥样硬化形成并可能降低糖尿病斑块稳定性。(C)2003爱思唯尔科学爱尔兰有限公司保留所有权利。
Diabetes is a major risk factor for atherosclerosis. Hyperglycemia is an underlying contributing factor; however, the mechanisms that mediate the vascular complications are not yet fully understood. In the present study, we provide evidence that elevated glucose induces discordant matrix metalloproteinase (MMP) expression from two key vascular cells, endothelial cells and macrophages. Our results clearly indicate that high glucose (25 mM) induced endothelial cell expression and activity of the collagenase, MMP-1 and the gelatinase, MMP-2, whilst reducing expression of the stromelysin, MMP-3 (P < 0.05). Similarly, our results show that high glucose (25 mM) induces expression and activity of MMP-9 from monocyte-derived macrophages (P < 0.05). High glucose culture did not affect metalloproteinase inhibitor (TIMP-1) expression. Our results suggest for the first time that high glucose exposure induced discordant regulation of the MMP/TIMP system in vascular cells. The increased MMP-1, MMP-2 and MMP-9 activities induced by high glucose exposure could promote matrix degradation thereby accelerating atherogenesis and potentially reducing plaque stability in diabetes. (C) 2003 Elsevier Science Ireland Ltd. All rights reserved.