Role of hepatic lipase in intermediate-density lipoprotein and small, dense low-density lipoprotein formation in hemodialysis patients.

ABSTRACT

BACKGROUND: It has been reported that remnant lipoproteins and small, dense low-density lipoproteins (LDLs) are risk factors for cardiovascular disease. To determine whether these risk factors are present in hemodialysis (HD) patients who are suffering from a high incidence of atherosclerotic vascular disease, we measured concentrations of remnant lipoproteins and LDL particle diameter in HD patients and compared these with controls. We also measured lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) that play important roles in the generation of remnant lipoproteins and small, dense LDL, and we correlated these changes with plasma lipoprotein abnormalities in HD patients. METHODS: Lipoproteins were separated by ultracentrifugation. Apoprotein B in very low-density lipoprotein (VLDL), and intermediate-density lipoprotein (IDL) fractions were measured by a sensitive enzyme-linked immunosorbent assay method. The average LDL particle diameter was measured by gradient gel electrophoresis. RESULTS: Plasma triglyceride, total cholesterol, and high-density lipoprotein (HDL) cholesterol concentrations were comparable between HD patients and controls, whereas LDL cholesterol was significantly lower in HD patients. The average LDL particle diameter was not significantly different between HD patients and controls. LDL particle diameter was inversely related to plasma triglyceride concentrations in all of the subjects. VLDL triglyceride, VLDL cholesterol, and VLDL apoprotein B were comparable between HD patients and controls. IDL triglyceride, IDL cholesterol, and IDL apoprotein B concentrations were all significantly increased in HD patients compared with those in controls. LPL mass was not altered, but HTGL activity was significantly decreased in HD patients. The HTGL activity was inversely related to IDL concentrations. CONCLUSIONS: These results suggest that a prominent characteristic of lipoprotein abnormalities in HD patients is a marked increase in IDL particle number. In addition, small, dense LDL is not associated with uremic dyslipidemia. Because HTGLs promote the conversion from IDL to LDL and the generation of lipid-poor LDL, a decrease in HTGL activity may contribute to the accumulation of IDL particle and may prevent small, dense LDL formation in HD patients.