Circulating Matrix Metalloproteinases and Their Inhibitors in Premature Coronary Atherosclerosis

Abstract

To investigate the clinical significance of circulating matrix metalloproteinases (MMPs) and their tissue inhibitos (TIMPs) in patients with premature coronary atheroscrelosis, we studied 53 consecutive male patients with angiographically defined premature (<65 years) and stable coronary artery disease. Plasma levels of MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 were determined in peripheral blood by a sandwich enzyme immunoassay, and the results were compared with those from 133 age-matched control males. There were significant 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) 27.2 +/- 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 +/- 171.4), 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 significant positive correlation between plasma MMP-9 levels and low-density lipoprotein (LDL)-cholesterol levels (Rs = 0.168, p = 0.022), and significant negative 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 = 0.0004) levels were positively correlated with HDL-cholesterol levels. TIMP-2 levels 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 that the circulating levels of MMPs and TIMPs are altered in patients with premature coronary atherosclerosis and that plasma lipoprotein cholesterol levels correlate with these, possibly as a result of the lipoprotein-vessel wall interactions.

Elevated MMP‐8 and Decreased Myeloperoxidase Concentrations Associate Significantly with the Risk for Peripheral Atherosclerosis Disease and Abdominal Aortic Aneurysm1

“…MMP-8 ⁄ TIMP-1 was significantly increased in patients with arterial disease. However, contradictory results whether the TIMP-1 associates with risk or not have been published [30,31]. TIMP-1 can damage the Figure 2 Receiver operating characteristicscurve for the prediction of arterial disease with various logistic models.…”

Effect of pronounced weight loss on the nontraditional cardiovascular risk marker matrix metalloproteinase-9 in middle-aged morbidly obese women

“…23 Furthermore, MMP-9 levels are increased in patients with premature atherosclerosis. 24 Thus, a reduction in MMP-9 levels might be beneficial and associated with a diminution in overall cardiovascular risk. Furthermore, IL-8 has been demonstrated to be a potential proatherogenic factor.…”

Biomarkers of Vascular Disease Linking Inflammation to Endothelial Activation

“…75 Circulating MMP-9 levels are increased in type 2 diabetic patients with coronary artery disease, and elevated serum MMP-9 concentrations, associated with decreased TIMP levels, have been linked to premature coronary atherosclerosis. 76,77 Recently, plasma MMP-9 concentration was identified as a predictor of cardiovascular mortality in patients with coronary artery disease. 78 Furthermore, the plaque-stabilizing effects of statins may be related to their ability to inhibit MMP-9 secretion.…”