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Electronegative low density lipoprotein (LDL(−)) is a minor modified fraction of LDL found in blood. It comprises a heterogeneous population of LDL particles modified by various mechanisms sharing as a common feature increased electronegativity. Modification by oxidation is one of these mechanisms. LDL(−) has inflammatory properties similar to those of oxidized LDL (oxLDL), such as inflammatory cytokine release in leukocytes and endothelial cells. However, in contrast with oxLDL, LDL(−) also has some anti-inflammatory effects on cultured cells. The inflammatory and anti-inflammatory properties ascribed to LDL(−) suggest that it could have a dual biological effect.

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.