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Native Matrix Metalloproteinase Characteristics May Influence Early Stenosis of Venous Versus Arterial Coronary Artery Bypass Grafting Conduits^*

^* From the Department of Surgery (Drs. Anstadt, Franga, Pennathur, Mawulawde, and Ms. Bannan), Vascular Biology Center, Medical College of Georgia, and Program in Clinical and Experimental Therapeutics (Drs. Portik-Dobos and Ergul), University of Georgia College of Pharmacy, Augusta, GA.

Correspondence to: Mark P. Anstadt, MD, FCCP, Department of Surgery, Medical College of Georgia, Augusta, GA 30912; e-mail: manstadt{at}mail.mcg.edu

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 immunoblotting 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.

Key Words: coronary artery bypass grafting surgery • internal mammary artery • matrix metalloproteinase • saphenous vein • vascular conduit

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