Circulating matrix metalloproteinases and their inhibitors in premature coronary atherosclerosis

To investigate the clinical significance of circulating matrix metalloprote inases (MMPs) and their tissue inhibitos (TIMPs) in patients with premature coronary atheroscrelosis, we studied 53 consecutive male patients with ang iographically defined premature (<65 years) and stable coronary artery dise ase. Plasma levels of MMP-2, MMP-3, MMP-9. TIMP-1. and TIMP-2 were determin ed in peripheral blood by a sandwich enzyme immunoassay, and the results we re compared with those from 133 age-matched control males. There were signi ficant differences in all the MMPs and TIMPs (p<0.001) between patients and controls. In the patient group, the levels of MMP-9 (mean +/- SD (ng/ml) 2 7.2 +/- 15.2/21.8 +/- 15.2) and TIMP-1 (130.4 +/- 55.7/94.5 +/- 26.3) were significantly higher, and the levels of MMP-2 (632.5 +/- 191.6/727.6 +/- 17 1.4). MMP-3 (53.1 +/- 31.2/79.6 +/- 29.9), and TIMP-2 (24.7 +/- 15.2/35.4 /- 16.4) were significantly lower than those of controls. We found signific ant positive correlation between plasma MMP-9 levels and low-density lipopr otein (LDL)-cholesterol levels (Rs=0.168, p=0.022), and significant negativ e correlation between plasma MMP-9 levels and high-density lipoprotein (HDL )-cholesterol levels (Rs=-0.164, p=0.026) by Spearman rank correlation test . In contrast, plasma MMP-2 (Rs=0.181, p=0.014) and MMP-3 (Rs=0.260, p=0.00 04) levels were positively correlated with HDL-cholesterol levels. TIMP-2 l evels were negatively correlated with total cholesterol (Rs=-0.197, p=0.007 ) and LDL-cholesterol (Rs=-0.168, p=0.022) levels. These results suggest th at the circulating levels of MMPs and TIMPs are altered in patients with pr emature coronary atherosclerosis and that plasma lipoprotein cholesterol le vels correlate with these, possibly as a result of the lipoprotein-vessel w all interactions.