Heavy Smoking Before Coronary Surgical Procedures Affects the Native Matrix Metalloproteinase-2 and Matrix Metalloproteinase-9 Gene Expression in Saphenous Vein Conduits

Abstract

Smoking has numerous effects that may promote atherosclerosis, but the pathogenesis of smoking-related vein graft disease after coronary artery bypass grafting (CABG) remains incompletely understood. Matrix metalloproteinase (MMP) subtypes MMP-2 and MMP-9 have been identified as the key components in vascular remodeling processes. However little is known about the native MMP2 and MMP9 gene expression in saphenous vein (SV) conduits of heavy smokers undergoing CABG. Two hundred eight patients were divided into 6 groups: nonsmokers, heavy smokers, 3-month quitters, 6-month quitters, 12-month quitters, and long-term quitters. mRNA and protein levels of MMP-2, MMP-9, and tissue inhibitors of metalloproteinases (TIMPs) 1 and TIMP-2 were analyzed. In a clinical study, SV graft patency after surgical procedures was followed up. Compared with the nonsmoker group, MMP2 and MMP9 gene expression was significantly increased in the other 5 groups (p < 0.05). In contrast to MMP response, TIMP1 and TIMP2 gene expression was significantly decreased (p < 0.05). An association of increased MMP2 and MMP9 gene expression with poor SV graft patency could be found in the clinical data from follow-up. Heavy smoking noticeably increases native MMP2 and MMP9 gene expression in the SV before CABG. Even after long-term cessation of smoking, the dysregulated MMP2 and MMP9 gene expression cannot recover to normal levels. With the elevated native MMP2 and MMP9 gene expression in the SV induced by heavy smoking, more vein graft disease can be found on long-term follow-up.