Normolipidaemic patients with coronary artery disease had significantly higher concentrations of chylomicron remnants in plasma than normolipidaemic subjects with normal coronary vessels. This may explain the mechanism underlying the susceptibility to atherosclerosis of coronary artery disease patients with normal fasting lipid values. As diet and drugs can ameliorate the accumulation of postprandial lipoproteins in plasma, the concentration of chylomicron remnants should be measured in patients at high risk of coronary artery disease.

Objective-ApoAV, a newly discovered apoprotein, affects plasma triglyceride level. To determine how this occurs, we studied triglyceride-rich lipoprotein (TRL) metabolism in mice deficient in apoAV. Methods and Results-No significant difference in triglyceride production rate was found between apoa5 Ϫ/Ϫ mice and controls. The presence or absence of apoAV affected TRL catabolism. After the injection of 14 C-palmitate and 3 H-cholesterol labeled chylomicrons and 125 I-labeled chylomicron remnants, the disappearance of 14 C, 3 H, and 125 I was significantly slower in apoa5 Ϫ/Ϫ mice relative to controls. This was because of diminished lipolysis of TRL and the reduced rate of uptake of their remnants in apoa5 Ϫ/Ϫ mice. Observed elevated cholesterol level was caused by increased high-density lipoprotein (HDL) cholesterol in apoa5 Ϫ/Ϫ mice. VLDL from apoa5 Ϫ/Ϫ mice were poor substrate for lipoprotein lipase, and did not bind to the low-density lipoprotein (LDL) receptor as well as normal very-low-density lipoprotein (VLDL). LDL receptor levels were slightly elevated in apoa5 Ϫ/Ϫ mice consistent with lower remnant uptake rates. These alterations may be the result of the lower apoE-to-apoC ratio found in VLDL isolated from apoa5 Ϫ/Ϫ mice. Key Words: Apoa5 Ⅲ hypertriglyceridemia Ⅲ knockout Ⅲ lipolysis Ⅲ triglyceride-rich lipoproteins T he level of triglycerides in the blood has been correlated with the risk of atherosclerosis in a variety of studies. 1,2 Apoproteins of triglyceride-rich lipoproteins (TRL) play an important role in triglyceride transport. In particular, ApoCs and apoE 3,4 strongly affect TRL metabolism and thus plasma triglyceride levels. ApoAV is a newly discovered apolipoprotein, which was identified independently by 2 groups. 5,6 Disruption of the apoa5 gene in mice resulted in hypertriglyceridemia, whereas overexpression led to decreased plasma triglyceride concentrations, thus establishing an important role for this protein in triglyceride homeostasis. 5 One explanation for apoAV's lack of earlier identification is its low plasma concentration (Ϸ1 g/mL), which may be in part caused by the observation that during its synthesis, it is largely retained in the endoplasmic reticulum and does not traffic to the Golgi. 7,8 Furthermore, the low concentration of apoAV in plasma suggests that either this protein does not exert its effect in plasma or that it has a very potent effect on lipoprotein particle composition and/or metabolism. Several studies in humans 9 revealed strong associations between APOA5 polymorphisms and triglyceride levels. Most striking was the association between the minor APOA5 haplotypes found in 25% to 50% of whites, blacks, and Hispanics, and increased plasma triglyceride levels. To better understand the specific mechanisms by which altered apoAV exerts its effect on triglyceride levels in humans and mice, we studied the metabolism of TRL in vivo in mice lacking apoAV. Conclusions-These See page 2445ApoAV could influence triglyceride levels through alterations in the hepatic triglycer...

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Abstract:Background: Excess cholesterol is usually eliminated from the body by conversion to bile acids excreted in feces as bile salts. The excretion of large amounts of bile protects against atherosclerosis, while diminished excretion may lead to coronary artery disease (CAD). Objective: To investigate a relationship between CAD and bile acid excretion. Methods: Bile acid excretion was compared between 36 patients with proven CAD and 37 CAD-free individuals (controls). The groups were comparable for demographics and selected risk factors. All subjects received a 4-day standard diet that included $500 mg of cholesterol. Fecal bile acids from 24-hour stool collections were measured by gas liquid chromatography. Results: CAD patients excreted lower amounts of total bile acids (358±156 mg) than controls (617±293 mg; p < 0.01) and less deoxycholic acid (188.29±98.12 mg versus 325.96±198.57 mg; p < 0.0001) and less lithocholic acid (115.43±71.89 mg versus 197.27±126.87 mg; p < 0.01). Advanced age, male gender, left ventricular ejection fraction and total bile acid levels were significant independent factors that predicted CAD (p < 0.05). Mortality, CAD and cerebrovascular accident development rates were significantly lower for the controls at the 13-year follow up. Conclusion: CAD patients have significantly decreased bile acid excretion levels than non-CAD patients. An impaired ability to excrete cholesterol may be an additional risk factor for CAD development.

Background: Rats with chronic renal failure have a low nitric oxide (NO) production and a diminished NO excretion. The supplementation of L-arginine has an inhibitory effect on the progression of renal insufficiency. Methods: The present study was designed to determine whether chronic renal failure patients have a low NO production. Plasma and urine nitrate (NO₃) and nitrite (NO₂), stable metabolites of NO, were measured in 83 consecutive patients with chronic renal failure. The 83 chronic renal failure patients were divided into three groups: group 1, mild renal failure (creatinine clearance >60 ml/min/1.73 m²); group 2, moderate renal failure (creatinine clearance >30 <60 ml/min/1.73 m²), and group 3, severe renal failure (creatinine clearance <30 ml/min/1.73 m²). Thirty-three healthy volunteers served as controls. Results: The daily urinary NO excretion was significantly lower in patients with moderate and severe renal failure as compared with those with mild renal failure and normal controls. The lowest values were found in the severe renal failure group. When the 24-hour urinary NO excretion or NO per milligram creatinine and the NO clearance were correlated with the renal function in all patients as a group, these parameters were directly correlated with the creatinine clearance and inversely correlated with the serum creatinine level. The plasma NO concentration was not different between the three chronic renal failure groups, but higher than in the controls. Plasma NO in renal failure patients was not correlated with the creatinine clearance or serum creatinine levels. Conclusions: Chronic renal failure is a state of NO deficiency. Treatment strategies to increase NO production (L-arginine supplementation or other NO compounds) may prove to be useful in maintaining the renal function and slow the progression of renal disease.

The RS-205 is suitable for monitoring patients at high risk of CPE development. It enables detection of CPE and the monitoring of patients at all stages of CPE.

This study was undertaken to examine the possible role of endothelium-derived relaxing factor (EDRF), identified as nitric oxide (NO), in the pathogenesis of radiocontrast-induced acute renal failure in rats. Normal and salt-depleted rats were monitored for 60 min or 24 h after radiocontrast administration. The administration of L-arginine to normal rats abolished the immediate decrease in p-aminohippurate clearance (CPAH) and attenuated the decrease in inulin clearance (CIn). The administration of NO synthase inhibitor to the salt-depleted animals resulted in a significantly more pronounced decrease in CPAH compared with both the control and the L-arginine-treated animals. The recovery of CIn 24 h after radiocontrast administration to the salt-depleted rats was significantly better in the L-arginine-treated rats than in either the control or inhibitor-treated groups. The administration of radiocontrast material resulted in a significant decrease in urinary guanosine 3',5'-cyclic monophosphate as well as NO2 + NO3 excretion. This decrease was significantly attenuated by L-arginine. Our results 1) suggest that NO plays a major role in the pathogenesis of radiocontrast-induced acute renal failure and 2) suggest a novel therapeutic approach, i.e., the use of L-arginine in this form of acute renal failure.