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Objective: Pigment epithelium-derived factor (PEDF) is a potent inhibitor of angiogenesis and an important target molecule for preventing the progression of atherosclerosis. However, the relationship between PEDF and coronary atherosclerosis has not been fully examined. The aim of the present study is to evaluate the effects of statins on serum PEDF levels and the association between PEDF and coronary atherosclerosis., Patients and Methods: Coronary atherosclerosis in nonculprit lesions in the vessel of patients undergoing a percutaneous coronary intervention was evaluated using virtual histology intravascular ultrasound in 99 patients during percutaneous coronary intervention and after 8 months of statin therapy., Results: Serum PEDF levels at baseline and at the 8-month follow-up did not differ. A significant decrease in the fibro-fatty component (-0.24 mm³/mm, P=0.0003) and increases in the necrotic core (0.13 mm³/mm, P=0.02) and dense calcium components (0.11 mm³/mm, P<0.0001) were observed during the 8-month statin therapy. On univariate regression analyses, serum PEDF levels (r=0.291, P=0.004) and unstable angina pectoris (r=0.203, P=0.04) showed significant positive correlations with the percentage change in necrotic core volume. Multivariate regression analysis showed that serum PEDF level was a significant independent predictor associated with necrotic core progression during statin therapy (β=0.218, P=0.04)., Conclusion: Statin therapy had no effects on serum PEDF levels. Serum PEDF was a useful biomarker for predicting necrotic core progression during statin therapy, and its levels could be elevated as a counter-regulatory response mechanism to protect against necrotic core progression.

Objective: The role of serum uric acid (UA) in the pathophysiology of atherosclerosis is ambiguous and remains controversial. The purpose of the present study was to evaluate the relationship between serum UA and coronary atherosclerosis., Patients and Methods: Coronary atherosclerosis in the nonculprit lesions was evaluated using virtual histology intravascular ultrasound in 119 patients with angina pectoris at the time of percutaneous coronary intervention and 8 months after statin therapy., Results: Serum UA levels showed weak but significant positive correlations with external elastic membrane volume (baseline: r=0.236, P=0.02; 8-month follow-up: r=0.307, P=0.0009) and with plaque volume (baseline: r=0.263, P=0.007; 8-month follow-up: r=0.349, P=0.0001). Significant decreases in the fibrofatty and fibrous components and increases in the necrotic core and dense calcium components were observed during statin therapy. Serum UA (r=0.257, P=0.009) and unstable angina pectoris (r=0.208, P=0.02) correlated significantly with change in the calcified plaque volume, whereas the estimated glomerular filtration rate trended (r=-0.166, P=0.07). Multivariate regression analyses showed that UA was a significant independent predictor associated with an increase in the dense calcium plaque volume during statin therapy (β=0.244, P=0.03)., Conclusion: In this preliminary study, serum UA levels correlated with coronary atherosclerosis before and during statin therapy. It remains unknown whether these correlations are a direct effect of UA itself or a marker of increased risk.

Objective: Recent trials using intravascular ultrasound (IVUS) have shown that statins induce regression and stabilization of coronary artery plaques. However, there are no reports on whether regression and stabilization in coronary artery plaques associated with statin therapy continue or not. The purpose of the present study was to examine the time course of statin-induced changes in coronary atherosclerosis., Patients and Methods: Coronary atherosclerosis was evaluated using virtual histology-IVUS in 39 patients at the time of a percutaneous coronary intervention, 8 months after statin therapy (mid-term), and at 48-month (long-term) follow-up. IVUS images qualified for evaluation obtained from 30 of these patients at three time points., Results: Significant decreases in low-density lipoprotein cholesterol and high-sensitivity C-reactive protein were observed at 8 months and these decreases continued for 48 months. A decrease in external elastic membrane volume was observed at 8 months (-1.1%) and reached significance at 48 months (-5.9%, P=0.0001). Plaque volume tended to decrease over time, but this was not statistically significant (-1.6% at 8 months and -3.8% at 48 months). An increase in the calcified plaque component was observed at 8 months (0.09±0.34 mm/mm) and reached significance at 48 months (0.21±0.33 mm/mm, P=0.002). Change in the calcified component and change in the external elastic membrane volume showed a significant negative correlation at the long-term follow-up (r=-0.598, P=0.0005)., Conclusion: Continued negative vessel remodeling associated with an increase in the calcified plaque component was observed following prolonged statin therapy by serial virtual histology-IVUS analysis.

This study was designed to investigate the effects of the angiotensin-converting enzyme (ACE) inhibitor quinapril and the angiotensin II-receptor antagonist losartan on insulin sensitivity in two types of genetic hypertensive rats with insulin resistance. Quinapril (3 mg/kg) and losartan (10 mg/kg) decreased the systolic blood pressure to almost the same extent in both spontaneously hypertensive rats (SHRs) and Dahl salt-sensitive (Dahl S) rats. Quinapril increased the glucose requirement for the euglycemic clamp test in both SHRs and Dahl S rats, whereas losartan increased it in SHRs but not in Dahl S rats. The severity of the metabolic abnormalities may be responsible for the failure of losartan to improve the insulin sensitivity in Dahl S rats because serum insulin, total cholesterol, triglyceride, and free fatty acids (FFAs) were higher in the Dahl S rats than in SHRs. A kinin antagonist, Hoe 140, inhibited the increase in the glucose requirement by quinapril without affecting the depressor effect of quinapril in SHRs. In conclusion, quinapril improved the insulin sensitivity more effectively than did losartan in the genetic hypertensive rats with insulin resistance and relatively severe metabolic abnormalities. Based on our findings, one of the mechanisms underlying the difference between quinapril and losartan may thus be endogenous kinins.

We measured plasma concentration of endothelin-1 in three children with Byler's disease, five with biliary atresia after portoenterostomy, and nine controls. No patients had ascites or hepatorenal syndrome. Plasma endothelin-1 levels were significantly higher in patients with Byler's disease than in the controls (5.19 +/- 0.90 versus 1.81 +/- 0.19 pg/ml, respectively; p < 0.01), but were normal in operated biliary atresia. Urinary concentrations of N-acetyl-beta-D-glucosaminidase (NAG) were significantly higher in the patients with Byler's disease than in controls. Plasma endothelin-1 level correlated significantly with serum concentration of bile acid (r = 0.91; p < 0.01) and urinary concentration of NAG (r = 0.92; p < 0.01). We conclude that plasma endothelin-1 levels are high in patients with severe biliary cirrhosis and that endothelin-1 may partially contribute to development of renal injury in cirrhosis.

To determine the relationship between low magnesium status and lipids, we divided 27 patients with microscopic hematuria and normal renal function into two groups according to magnesium retention, as measured by a magnesium-loading test, and compared their serum lipid and apolipoproteins. Patients with low magnesium status (n = 7) had significantly lower levels of cholesterol, HDL cholesterol, and apolipoprotein A-1 than those with normal magnesium status (n = 20); however, there were no significant differences between the groups in serum concentrations of magnesium and apolipoprotein B. These data suggest that magnesium deficiencies are associated with low serum concentration of HDL cholesterol and apolipoprotein A-1.

We determined the effects of cyclosporine on calcium, magnesium, and potassium metabolism in rats. Thirty Sprague-Dawley rats were randomized into three groups of ten animals each--control rats given olive oil, rats given cyclosporine at a dosage of 5 mg/kg daily, and rats given 15 mg/kg daily for four weeks. Urinary excretion of calcium, magnesium, and potassium was determined before and after 2 and 4 weeks of cyclosporine therapy. All rats were sacrificed after 4 weeks of therapy, and calcium, magnesium, and potassium concentrations in serum and tissues were determined. Serum magnesium levels were significantly lower in the cyclosporine-treated groups than in the control group, but there was no significant difference between the control and either of the cyclosporine-treated groups with regard to total urinary excretion of magnesium after four weeks of treatment. Magnesium content in the kidney, muscle, and liver was significantly higher in the 15 mg/kg group than in the control group. Calcium content in the kidney and liver was significantly higher as well. Potassium content in any type of tissue was similar in the three groups. We conclude that the intracellular migration of magnesium plays an important role--as does impaired renal conservation of magnesium--in the pathogenesis of cyclosporine-induced hypomagnesemia and that there is a discrepancy between magnesium and potassium metabolism in cyclosporine-treated rats.