Hepatic lipase- and endothelial lipase-deficiency in mice promotes macrophage-to-feces RCT and HDL antioxidant properties

Joan Carles Escolà-Gil, Xiangyu Chen, Josep Julve, Helena Quesada, David Santos, Jari Metso, Monica Tous, Matti Jauhiainen, Francisco Blanco-Vaca

Research output: Contribution to journalArticleResearchpeer-review

19 Citations (Scopus)

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 [3H]cholesterol-labeled mouse macrophages, after which the appearance of [3H]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 [3H]cholesterol 48 h after the label injection. The magnitude of macrophage-derived [3H]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. © 2013 Elsevier B.V.
Original languageEnglish
Pages (from-to)691-697
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1831
Issue number4
DOIs
Publication statusPublished - 1 Apr 2013

Keywords

  • apoA-I
  • Endothelial lipase
  • HDL
  • Hepatic lipase
  • Oxidation
  • Reverse cholesterol transport

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