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...

No abstract

Reduction of serum cholesterol levels with statin therapy decreases the risk of coronary heart disease. Inhibition of HMG-CoA reductase by statin results in decreased synthesis of cholesterol and other products downstream of mevalonate, which may produce adverse effects in statin therapy. We studied the reductions of serum ubiquinol-10 and ubiquinone-10 levels in hypercholesterolemic patients treated with atorvastatin. Fourteen patients were treated with 10 mg/day of atorvastatin, and serum lipid, ubiquinol-10 and ubiquinone-10 levels were measured before and after 8 weeks of treatment. Serum total cholesterol and LDL-cholesterol levels decreased significantly. All patients showed definite reductions of serum ubiquinol-10 and ubiquinone-10 levels, and mean levels of serum ubiquinol-10 and ubiquinone-10 levels decreased significantly from 0.81 ± ± ± ± ± 0.21 to 0.46 ± ± ± ± ± 0.10 µ µ µ µ µg/ml (p < 0.0001), and from 0.10 ± ± ± ± ± 0.06 to 0.06 ± ± ± ± ± 0.02 µ µ µ µ µg/ml (p = 0.0008), respectively. Percent reductions of ubiquinol-10 and those of total cholesterol showed a positive correlation (r = 0.627, p = 0.0165). As atorvastatin reduces serum ubiquinol-10 as well as serum cholesterol levels in all patients, it is imperative that physicians are forewarned about the risks associated with ubiquinol-10 depletion. J Atheroscler Thromb, 2005; 12: 111-119.

Abstract-To investigate the association of estrogen receptor (ER)-␣ gene polymorphisms with coronary artery disease (CAD), we studied 197 men and 98 postmenopausal women with heterozygous familial hypercholesterolemia. We examined the known polymorphisms, including PvuII, XbaI, TA repeat, and CA repeat, and identified 6 novel polymorphisms in the ER-␣ gene. The distributions of Ϫ1989T/G (a novel polymorphism in promoter B) and XbaI in intron 1 were associated with CAD in postmenopausal women and in men, with a higher frequency of the G/G genotype (Pϭ0.03) or X1/X1 genotype (Pϭ0.02) in the CAD group. The frequency of alleles of TA repeats Ͼ17 was found to be significantly higher in postmenopausal women with CAD than in those without CAD (Pϭ0.04), but not in men.Logistic regression analysis with all coronary risk factors as covariates showed that the G/G genotype was a higher risk for CAD (odds ratio 4.5, 95% CI 1.0 to 19.5; Pϭ0.04) but that X1/X1 was not. We conclude that Ϫ1989T/G or its linked polymorphisms in the ER-␣ gene may confer risk for CAD and that the G/G genotype may be an independent predictor for CAD in patients with familial hypercholesterolemia.