Relationship between MMP-1, MMP-9, TIMP-1, VEGF, IL-6 levels and the clinical presentation, severity of coronary artery disease and the coronary angiographic findings

Matrix metalloproteinases (MMPs) and Tissue Inhibitor of Matrix Metalloproteinases (TIMPs) which control the extracellular matrix degradation are thought to be associated with atherogenesis and plaque rupture. Vascular endothelial growth factor (VEGF) promotes the neoangiogenetic process within the plaque which renders it prone to rupture besides inflammation. The present study was designed to elucidate the relationship between MMP-1, MMP-9, TIMP-1, VEGF, IL-6 levels and the coronary angiographic extent and severity of atherosclerosis represented as Gensini score. In addition, any relationship between these biomarkers and TIMI Frame Count which shows epicardial blood flow, Myocardial Blush Grade which shows myocardial blood flow and Rentrop Collateral Score were investigated. It was also aimed to observe the difference of serum levels of these biomarkers in different clinical conditions.The serum concentrations of MMP-1, MMP-9, TIMP-1, VEGF and IL-6 were analyzed with ELISA method in 134 patients who had undergone coronary angiography. Patients were divided into five groups; stable angina pectoris (n= 34), unstable angina pectoris (n=29), non-ST elevation myocardial infarction (n=16), acute ST elevation myocardial infarction (n=25) and control (n=30). Coronary angiography was performed and Gensini Score, TIMI Score, TIMI Frame Count, Myocardial Blush Grade and Rentrop Collateral Score were assessed.MMP-1 levels were higher in STEMI and NSTEMI groups compared to unstable angina pectoris, stable angina pectoris and control groups (p<0,05). In STEMI group, MMP-9 levels were higher than USAP and control groups (p<0,05). IL-6 levels were higher in all groups than the control group and when clinical groups were compared with each other; STEMI and NSTEMI groups had higher levels (p<0,05). TIMP-1 levels were not significantly different within all five groups. MMP-1 levels were found to be elevated in diabetic patients (p:0,020); whereas MMP-9 levels were higher in smokers (p:0,043). The need for revascularisation by either coronary artery by-pass surgery or percutaneous coronary intervention was significantly related to higher MMP-1 and IL-6 levels; and this relation persisted after multivariate regression analysis (OR: 1,7 %95 CI:1,4-2,1; OR:6,5 %95 CI: 2,5-16). There were positive correlations between MMP-1, IL-6 and VEGF levels and angiographic Gensini Score which persisted after statistical corrections performed for possible confounders by multivariate regression analysis (r:0,71; 0,57; 0,39; p<0,001), (B:0,124 %95 CI:0,75-0,174; B:0,217 %95 CI:0,089-0,346; B:0,499 %95 CI:0,168-0,831). TIMI Frame Count and the absolute change in TIMI Frame Count after percutaneous coronary intervention were related to higher MMP-1 levels (r:0,7 p<0,001, r:0,47 p<0,001). Serum levels of MMP-1 and IL-6 were found to be negatively correlated with MBG (r:-0,57 p<0,001; r:-0,49 p<0,001). MMP-1 and VEGF levels were correlated with collateral score (r:0,6 p<0,001; r:0,57 p<0,001).