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.

ypertrophic cardiomyopathy (HCM) is characterized by disproportionate left ventricular (LV) hypertrophy and LV diastolic dysfunction. However, some patients with HCM develop LV wall thinning associated with LV dilatation and systolic dysfunction. [1][2][3][4][5][6][7] The pathological features reveal that such patients have myocardium with marked fibrosis and abnormal collagen matrices. 8 Evidence suggests that LV myocardial collagen matrix disorganization and changes in the fibrillar collagen network contribute to the progression of LV dilatation and dysfunction. 9,10 Matrix disorganization in LV dilatation has, in turn, been attributed to enhanced collagen degradation Circulation Journal Vol.68, April 2004 through changes in the concentrations of matrix metalloproteinases (MMPs) or their tissue inhibitors (TIMPs). [11][12][13] It has been suspected that the MMPs play an important role in tissue remodeling in both normal and pathological conditions. 14-22 Enhanced activity of MMPs could lead to increased collagen turnover and has been reported in idiopathic dilated cardiomyopathy (DCM), 19 tachycardiainduced heart failure 12,20 and pressure-overload hypertrophy. 13 Elevated concentrations of the serum markers of collagen turnover have also been reported in patients with idiopathic DCM. 21 Soejima et al showed a significant negative correlation between the concentration of serum MMP-1 and LV ejection fraction (LVEF). 22 Collectively, these findings suggest that changes in collagen metabolism may be associated with LV remodeling and the progression of LV systolic dysfunction in patients with HCM. However, the exact details and sequence of clinicopathological events remain uncertain.The present study was conducted in order to test the hypothesis that circulating MMPs and TIMPs may be altered in patients with HCM with systolic dysfunction and may be associated with LV remodeling in HCM. Methods and ResultsEnzyme-linked immunoassays were used to measure the plasma concentrations of MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 in 11 patients with HCM accompanied by systolic dysfunction (fractional shortening (FS) <25%, group A), 17 patients with HCM who had preserved systolic function (FS ≥25%, group B), and 50 age-matched clinically healthy control subjects (mean age: 57 years). The concentration of MMP-2 in group A was significantly higher than in group B and the control subjects (1,124±84, 792±49, 809±26 ng/ml, respectively), whereas there was no significant difference between group B and the control subjects. MMP-2 concentrations significantly increased as the New York Heart Association functional class increased in patients with HCM. TIMP-2 was also significantly higher in group A patients than in group B and the control subjects (45.3±4.7, 34.6±2.2, 33.7±1.8 ng/ml, respectively), but there was no difference between group B and control subjects. TIMP-1 was significantly higher in HCM patients than in control subjects. MMP-3 and MMP-9 concentrations did not differ among the 3 groups. Both MMP-2 and TIMP-2 correlat...

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Lung cancer is the leading cause of death from cancer in Japan. Studies in other countries have reported a venous thromboembolism (VTE) rate of 4%–20% in cancer patients. In this study, we aimed to determine the incidence of VTE in lung cancer patients in Japan and compared the characteristics of patients with and without VTE. In this retrospective cohort study, the clinicopathological characteristics of study patients with and without concomitant VTE were compared. Patients with lung cancer treated at Fukui Prefectural Hospital, Japan from 2008 to 2017. Of the 1471 patients with lung cancer studied, 28 developed VTE. Five patients developed pulmonary thromboembolism (PTE) alone, 9 PTE with concomitant deep vein thrombosis, and 14 deep vein thrombosis alone. Compared with patients in the non-VTE group, the VTE group was significantly younger (mean value ± SD 66.3 ± 10.1 vs. 73.0 ± 10.6 years, p = 0.001), contained significantly more patients with stage IIIb–IV disease (p = 0.002), and had a significantly higher rate of chemotherapy (p < 0.001) and radiation therapy (p = 0.007). There was no significant difference in median survival time from lung cancer diagnosis between the VTE and non-VTE groups. The 1-year mortality rate after VTE diagnosis was 60.7%. Lung cancer was the most frequent cause of death, followed by infection and VTE. Several baseline characteristics differed between patients with and without VTE. The prognosis may worsen after development of VTE, suggesting that lung cancer patients should be carefully monitored for it.

Familial hypercholesterolemia (FH) results from low-density lipoprotein (LDL) receptor gene mutations. Heterozygotes have twice normal LDL-cholesterol concentrations in early childhood, and experience early myocardial infarction. We demonstrated bimodal cholesterol frequency distributions, independently confirming existence of an identifiable hypercholesterolemic subpopulation. We assayed blood lipids in 181 FH patients genetically diagnosed and 100 unaffected relatives. Receiver operating characteristics curves were constructed. Total cholesterol and LDL-cholesterol concentrations showed bimodality. A total cholesterol cutoff of 225 mg/dl produced results agreeing with DNA testing (specificity, 98.5%; sensitivity, 99.4%). An LDL-cholesterol cutoff of 161-163 mg/dl produced 98.5% specificity and 98.3% sensitivity. Areas under curves were 0.9826 ± ± ± ± ± 0.0058 for total cholesterol, and 0.9852 ± ± ± ± ± 0.0043 for LDLcholesterol. In conclusion, we define total cholesterol and LDL-cholesterol levels of 225 and 160 mg/dl, respectively, as cutoff points of normal subjects and FH patients. J Atheroscler Thromb, 2005; 12: 35-40.