Abstract 827: Role of Endothelial Lipase in Low Serum High-Density Lipoprotein (HDL) Level Associated with Hypertriglyceridemia
Objectives: Patients with hypertriglyceridemia often have low plasma HDL levels. However, the correlation between high triglyceride (TG) and low HDL has not been fully understood. Endothelial lipase (EL) is a physiological determinant of plasma HDL level. Poloxamer-407 (P407) is a non-ionic surfactant which induces TG-dominant hyperlipidemia in mice by inhibiting lipoprotein lipase (LPL) and hepatic lipase (HL). We aimed to clarify the potential role for EL in low HDL associated with hypertriglyceridemia using this model.
Methods: To establish TG-dominant hyperlipidemia, EL-deficient mice (EL−/−) and wild-type C57Bl6/J mice (WT) were injected with P407 (0.5g/kg, i.p.), and plasma lipoprotein profiles were analyzed by ultracentrifuge and gel filtration chromatography assays.
Results: A single injection of P407 resulted in the dramatical increase in plasma TG together with the decrease in HDL-C level both in WT and EL−/−, which resembled the type IV hyperlipidemia in humans. Although plasma TG levels after P407 injection were similar between EL−/− and WT, the HDL-C level in EL−/− was 80% higher and the HDL particle size was significantly larger in EL−/− when compared with those in WT. In contrast that LPL and HL activity was inhibited by >95% by P407, EL phospholipase activity was substantially detectable in WT after P407 treatment. P407 per se did not affect EL expression in mouse tissues and in cultured endothelial cells. There was no difference in CETP activity before and after the P407 injection between EL−/− and WT.
Conclusions: EL regulates plasma HDL level in hypertriglyceridemia, irrespective of the plasma TG level, LPL, HL, and CETP activities. Thus, EL may be responsible for the genesis of the low HDL level associated with hypertriglyceridemia. Considering that EL inactivation in vivo increased the HDL level in hypertriglyceridemic mice, EL would be a novel target for HDL-raising intervention in metabolic syndrome.