Relationship Between MMP-1, MMP-9, TIMP-1, IL-6 and Risk Factors, Clinical Presentation, Extent and Severity of Atherosclerotic Coronary Artery Disease

BACKGROUND: Matrix metalloproteinases (MMPs) and Tissue Inhibitor of Matrix Metalloproteinases (TIMPs) may be associated with atherogenesis and plaque rupture. We evaluated the relationship between MMP-1, MMP-9, TIMP-1 and IL-6 levels and risk factors, presentation, extent and severity of atherosclerotic coronary artery disease (CAD). METHODS: Consecutive patients who underwent coronary angiography were randomly included. The serum concentrations of MMP-1, MMP-9, TIMP-1 and IL-6 were analyzed with ELISA method in 134 patients. Participants were divided into 5 groups; stable angina pectoris (SAP; n= 34), unstable angina pectoris (USAP; n=29), non-ST elevation myocardial infarction (NSTEMI; n=16), acute ST elevation myocardial infarction (STEMI; n=25) and controls (n=30). Coronary angiographic Gensini score was calculated. RESULTS: MMP-1 levels were higher in STEMI and NSTEMI groups compared with USAP, SAP and control groups (STEMI vs USAP p=0.005; STEMI vs SAP p=0.001; STEMI vs control p<0.001; NSTEMI vs USAP p=0.02; NSTEMI vs SAP p=0.027; NSTEMI vs control p<0.001). In STEMI group, MMP-9 levels were higher than USAP and control groups (p=0.002; p<0,001). TIMP-1 levels were not significantly different within all 5 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). Higher MMP-1, MMP-9 and IL-6 levels were correlated with severe Left Anterior Descending artery (LAD) stenosis and higher angiographic Gensini Score (for severe LAD stenosis; r = 0.671, 0.363, 0.509 p<0.001; for Gensini score; r = 0.717, 0.371, 0.578 p<0.001). CONCLUSIONS: Serum levels of MMP-1, MMP-9, and IL-6 are elevated in patients with CAD; more so in acute coronary syndromes. MMP-1, MMP-9 and IL-6 are associated with more extensive and severe CAD (as represented by Gensini score).