title: 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.
authors: The Second Department of Internal Medicine, School of Medicine, Kanazawa University, Japan. nojinoji@im2.m.kanazawa-u.ac.jp
authors: Y
authors: Y
authors: Noji
authors: K
authors: K
authors: Kajinami
authors: M A
authors: MA
authors: Kawashiri
authors: Y
authors: Y
authors: Todo
authors: T
authors: T
authors: Horita
authors: A
authors: A
authors: Nohara
authors: T
authors: T
authors: Higashikata
authors: A
authors: A
authors: Inazu
authors: J
authors: J
authors: Koizumi
authors: T
authors: T
authors: Takegoshi
authors: H
authors: H
authors: Mabuchi
mesh_terms: D015415:Biomarkers / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood*; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood*; D008875:Middle Aged; D011480:Protease Inhibitors / Q000097:blood*; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood*; D014280:Triglycerides / Q000097:blood
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids; D011480:Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D014280:Triglycerides; D020782:Matrix Metalloproteinases