TY - JOUR
T1 - Native matrix metalloproteinase characteristics may influence early stenosis of venous versus arterial coronary artery bypass grafting conduits
AU - Anstadt, Mark P.
AU - Franga, Dion L.
AU - Portik-Dobos, Vera
AU - Pennathur, Arjun
AU - Bannan, Mary
AU - Mawulawde, Kwabena
AU - Ergul, Adviye
N1 - Funding Information:
This study was supported by grants from American Heart Association, American Diabetes Association, and Pfizer Atorvastatin Research Program to Dr. Ergul, and Medical College of Georgia/University of Georgia Combined Intramural Research Grant to Drs. Ergul and Anstadt.
PY - 2004/5
Y1 - 2004/5
N2 - 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 CABC 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.
AB - 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 CABC 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.
KW - Coronary artery bypass grafting surgery
KW - Internal mammary artery
KW - Matrix metalloproteinase
KW - Saphenous vein
KW - Vascular conduit
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U2 - 10.1378/chest.125.5.1853
DO - 10.1378/chest.125.5.1853
M3 - Article
C2 - 15136400
AN - SCOPUS:2442511808
SN - 0012-3692
VL - 125
SP - 1853
EP - 1858
JO - CHEST
JF - CHEST
IS - 5
ER -