Abstract: Electronegative low-density lipoprotein (LDL(−)) is a minor modified LDL subfraction that is present in blood. LDL(−) promotes inflammation and is associated with the development of atherosclerosis. We previously reported that the increase of cytokine release promoted by this lipoprotein subfraction in monocytes is counteracted by high-density lipoprotein (HDL). HDL also inhibits a phospholipase C-like activity (PLC-like) intrinsic to LDL(−). The aim of this work was to assess whether the inhibition of the PLC-like activity by HDL could decrease the content of ceramide (CER) and diacylglycerol (DAG) generated in LDL(−). This knowledge would allow us to establish a relationship between these compounds and the inflammatory activity of LDL(−). LDL(−) incubated at 37 °C for 20 h increased its PLC-like activity and, subsequently, the amount of CER and DAG. We found that incubating LDL(−) with HDL decreased both products in LDL(−). Native LDL was modified by lipolysis with PLC or by incubation with CER-enriched or DAG-enriched liposomes. The increase of CER in native LDL significantly increased cytokine release, whereas the enrichment in DAG did not show these inflammatory properties. These data point to CER, a resultant product of the PLC-like activity, as a major determinant of the inflammatory activity induced by LDL(−) in monocytes.
Keywords: electronegative LDL; HDL; cytokines; ceramide; diacylglycerol; lipoprotein aggregation; monocytes; phospholipase C
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Estruch, M.; Sanchez-Quesada, J.L.; Beloki, L.; Ordoñez-Llanos, J.; Benitez, S. The Induction of Cytokine Release in Monocytes by Electronegative Low-Density Lipoprotein (LDL) Is Related to Its Higher Ceramide Content than Native LDL. Int. J. Mol. Sci. 2013, 14, 2601-2616.
Estruch M, Sanchez-Quesada JL, Beloki L, Ordoñez-Llanos J, Benitez S. The Induction of Cytokine Release in Monocytes by Electronegative Low-Density Lipoprotein (LDL) Is Related to Its Higher Ceramide Content than Native LDL. International Journal of Molecular Sciences. 2013; 14(2):2601-2616.
Estruch, Montserrat; Sanchez-Quesada, Jose L.; Beloki, Lorea; Ordoñez-Llanos, Jordi; Benitez, Sonia. 2013. "The Induction of Cytokine Release in Monocytes by Electronegative Low-Density Lipoprotein (LDL) Is Related to Its Higher Ceramide Content than Native LDL." Int. J. Mol. Sci. 14, no. 2: 2601-2616.