Native matrix metalloproteinase characteristics may influence early stenosis of venous versus arterial coronary artery bypass grafting conduits
Native matrix metalloproteinase characteristics may influence early stenosis of venous versus arterial coronary artery bypass grafting conduits
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DOI：
10.1378/chest.125.5.1853
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发表时间：
2004-05-01
期刊：
影响因子：
9.6
通讯作者：
Ergul, A
中科院分区：
文献类型：
--
作者：
Anstadt, MP;Franga, DL;Ergul, A
目的：乳内动脉（IMA）和隐静脉（SV）冠状动脉旁路移植术（cabg）狭窄和闭塞率有显著差异，这是由于血管重构的差异造成的。基质金属蛋白酶（MMPs）和金属蛋白酶组织抑制剂（TIMPs）调节血管结构，并可能对移植物通畅有重要影响。然而，IMA和SV的MMP环境和表达谱尚未对比。因此，本研究的目的是评估和比较IMA和SV导管中的原生MMP系统。方法：取冠脉搭桥患者IMA （n = 10）和SV （n = 10）标本。MMP-1、MMP-2和MMP-9、TIMP-1、膜结合MMP激活剂（MT1-MMP）和细胞外MMP诱导蛋白（EMMPRIN）的蛋白水平通过免疫印迹法测定，并通过密度分析定量。明胶酶谱法测定MMP-2和MMP-9活性。结果：SV（2218 +/- 351像素）的MMP-2水平明显高于IMA（1012 +/- 213像素）标本（平均+/- SEM）。MMP-1、MMP-9、TIMP-1含量差异无统计学意义；然而，MT1-MMP和EMMPRIN水平在SV中（847 +/- 190像素，1742 +/- 461像素）明显低于IMA导管（2590 + 403像素，5606 + 678像素）（p < 0.05）。在SV和IMA样品中，MMP-9活性相似，而MMP-2活性显著增加。结论：SV和IMA导管含有相同的MMP分子成分。然而，与IMA相比，SV的MMP-2水平和活性明显更丰富。这些差异可能有助于冠脉搭桥术后SV和IMA导管的早期病理性重构。
Purpose: Stenosis and occlusion rates of internal mammary artery (IMA) and saphenous vein (SV) coronary artery bypass grafts (CABGs) are markedly different, which result from respective disparities in vascular remodeling. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate vascular structure and may have important influence on graft patency. However, the MMP milieu and expression profile of the IMA and SV have not been contrasted. Therefore, the aim of this study was to assess and compare the native MMP systems in IMA vs SV conduits.Methods: IMA (n = 10) and SV (n = 10) specimens were obtained from patients undergoing CABG surgery. Protein levels of MMP-1, MMP-2, and MMP-9, TIMP-1, a membrane-bound MMP activator (MT1-MMP), and an extracellular MMP inducer protein (EMMPRIN) were determined by immuno-blotting and quantified by densitometric analysis. MMP-2 and MMP-9 activity was determined by gelatin zymography.Results: MMP-2 levels were significantly higher in SV (2,218 +/- 351 pixels) vs IMA (1,012 +/- 213 pixels) specimens (mean +/- SEM]). There were no significant differences in MMP-1, MMP-9, or TIMP-1 content; however, MT1-MMP and EMMPRIN levels were significantly lower in SV (847 +/- 190 pixels, 1,742 +/- 461 pixels) vs IMA conduits (2,590 + 403 pixels, 5,606 + 678 pixels), respectively (p < 0.05). MMP-9 activity was similar while MMP-2 activity was significantly increased in SV vs IMA specimens.Conclusions: SV and IMA conduits harbor the same MMP molecular constituents. However, MMP-2 levels and activity are significantly more abundant in the SV compared to the IMA. These differences may contribute to the early pathologic remodeling of the SV vs IMA conduit following CABG surgery.