title: Hepatic lipase- and endothelial lipase-deficiency in mice promotes macrophage-to-feces RCT and HDL antioxidant properties.
abstract: Hepatic lipase (HL) and endothelial lipase (EL) are negative regulators of plasma HDL cholesterol (HDLc) levels and presumably could affect two main HDL atheroprotective functions, macrophage-to-feces reverse cholesterol transport (RCT) and HDL antioxidant properties. In this study, we assessed the effects of both HL and EL deficiency on macrophage-specific RCT process and HDL ability to protect against LDL oxidation. HL- and EL-deficient and wild-type mice were injected intraperitoneally with [(3)H]cholesterol-labeled mouse macrophages, after which the appearance of [(3)H]cholesterol in plasma, liver, and feces was determined. The degree of HDL oxidation and the protection of oxidative modification of LDL co-incubated with HDL were evaluated by measuring conjugated diene kinetics. Plasma levels of HDLc, HDL phospholipids, apoA-I, and platelet-activated factor acetyl-hydrolase were increased in both HL- and EL-deficient mice. These genetically modified mice displayed increased levels of radiolabeled, HDL-bound [(3)H]cholesterol 48h after the label injection. The magnitude of macrophage-derived [(3)H]cholesterol in feces was also increased in both the HL- and EL-deficient mice. HDL from the HL- and EL-deficient mice was less prone to oxidation and had a higher ability to protect LDL from oxidation, compared with the HDL derived from the wild-type mice. These changes were correlated with plasma apoA-I and apoA-I/HDL total protein levels. In conclusion, targeted inactivation of both HL and EL in mice promoted macrophage-to-feces RCT and enhanced HDL antioxidant properties.
authors: IIB Sant Pau. 08025 Barcelona, Spain. jescola@santpau.cat
authors: Joan Carles
authors: JC
authors: Escolà-Gil
authors: Xiangyu
authors: X
authors: Chen
authors: Josep
authors: J
authors: Julve
authors: Helena
authors: H
authors: Quesada
authors: David
authors: D
authors: Santos
authors: Jari
authors: J
authors: Metso
authors: Monica
authors: M
authors: Tous
authors: Matti
authors: M
authors: Jauhiainen
authors: Francisco
authors: F
authors: Blanco-Vaca
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000097:blood; D001692:Biological Transport / Q000502:physiology; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood; D005243:Feces / Q000737:chemistry*; D008049:Lipase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000097:blood; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010084:Oxidation-Reduction
chemical_list: D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D002784:Cholesterol; D008049:Lipase; C495700:Lipc protein, mouse; C498741:Lipg protein, mouse