Evidence for a matrix metalloproteinase induction/activation system in arterial vasculature and decreased synthesis and activity in diabetes
Evidence for a matrix metalloproteinase induction/activation system in arterial vasculature and decreased synthesis and activity in diabetes
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DOI：
10.2337/diabetes.51.10.3063
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发表时间：
2002-10-01
期刊：
影响因子：
7.7
通讯作者：
Ergul, A
中科院分区：
文献类型：
--
作者：
Portik-Dobos, V;Anstadt, MP;Ergul, A
以细胞外基质（ECM）沉积为特征的病理性重构是糖尿病血管并发症的重要原因。基质金属蛋白酶（MMP）调节ECM周转。然而，MMP系统在糖尿病人体组织中的表达谱仍然未知。本研究的目的是：1）鉴定动脉血管系统中存在的局部MMP诱导/激活系统; 2）确定MMP系统在糖尿病中如何改变。乳内动脉标本取自糖尿病患者（n = 14）和非糖尿病患者（n = 14），这些患者正在接受冠状动脉旁路移植术。ECM诱导蛋白（EMMPRIN）;膜型MMP（MT-MMP）;和MMP-1，-2，和-9通过免疫印迹和密度扫描（像素）进行定量。Pro-MMP-1和MMP-2在糖尿病组织中的表达分别由非糖尿病组织的952120和1081508 pixel下降到糖尿病组织的39862和24942 pixel（P < 0.05）。EMMPRIN、MT-MMP表达及总MMP活性在糖尿病组均降低2倍（P < 0.05）。这些结果首次证明MMP诱导和激活系统存在于人动脉血管系统中，并且在糖尿病中下调。MMP活性降低可能导致糖尿病胶原沉积增加和病理性重塑。
Pathological remodeling characterized by extracellular matrix (ECM) deposition contributes to the diabetic vascular complications. Matrix metalloproteinases (MMPs) regulate ECM turnover. However, the expression profile of the MMP system in diabetic human tissue remains unknown. The objectives of this study were 1) to identify a local MMP induction/activation system that exists in arterial vasculature and 2) to determine how the MMP system may be altered in diabetes. Internal mammary artery specimens were obtained from patients who did (n = 14) and did not (n = 14) have diabetes and were undergoing coronary artery bypass grafting surgery. ECM inducer protein (EMMPRIN); membrane-type MMP (MT-MMP); and MMP-1, -2, and -9 were quantified by immunoblotting and densitometric scanning (pixels). Pro-MMP-1 and MMP-2 levels were decreased from 952 120 and 1,081 508 pixels, respectively, in nondiabetic tissue to 398 62 and 249 42 pixels in the diabetic tissue (P < 0.05). Both EMMPRIN and MT-MMP expression and total MMP activity were decreased by twofold in diabetic patients (P < 0.05). These results demonstrated for the first time that an MMP induction and activation system exists in human arterial vasculature and that it is downregulated in diabetes. Decreased MMP activity may contribute to increased collagen deposition and pathological remodeling in diabetes.