Abstract
Electronegative LDL [LDL(-)] is a minor modified LDL subfraction present in blood with inflammatory effects. One of the antiatherogenic properties of HDL is the inhibition of the deleterious effects of in vitro modified LDL. However, the effect of HDL on the inflammatory activity of LDL(-) isolated from plasma is unknown. We aimed to assess the putative protective role of HDL against the cytokine released induced in monocytes by LDL(-). Our results showed that LDL(-) cytokine release was inhibited when LDL(-) was coincubated with HDL and human monocytes and also when LDL(-) was preincubated with HDL and reisolated prior to cell incubation. The addition of apoliprotein (apo)AI instead of HDL reproduced the protective behavior of HDL. HDL preincubated with LDL(-) promoted greater cytokine release than native HDL. Incubation of LDL(-) with HDL decreased the electronegative charge, phospholipase C-like activity, susceptibility to aggregation and nonesterified fatty acid (NEFA) content of LDL(-), whereas these properties increased in HDL. NEFA content in LDL appeared to be related to cytokine production because NEFA-enriched LDL induced cytokine release. HDL, at least in part through apoAI, inhibits phospholipase-C activity and cytokine release in monocytes, thereby counteracting the inflammatory effect of LDL(-). In turn, HDL acquires these properties and becomes inflammatory.
Highlights
Electronegative LDL [LDL(–)] is a minor modified LDL subfraction present in blood with inflammatory effects
Prevents the effect of oxidized LDL and minimally modified LDL [6, 7]; our findings show that HDL neutralizes LDL(–), an inflammatory particle that is isolable from plasma and does not present a higher level of oxidation than native LDL [15]
The properties of LDL(–) differ considerably from those of minimally modified LDL (mmLDL) because LDL(–) presents platelet-activating factor acetylhydrolase (PAF-AH) and phospholipase C (PLC)-like activity and high binding to proteoglycans whereas mmLDL does not
Summary
Electronegative LDL [LDL(–)] is a minor modified LDL subfraction present in blood with inflammatory effects. We aimed to assess the putative protective role of HDL against the cytokine released induced in monocytes by LDL(–). Incubation of LDL(–) with HDL decreased the electronegative charge, phospholipase C-like activity, susceptibility to aggregation and nonesterified fatty acid (NEFA) content of LDL(–), whereas these properties increased in HDL. HDL, at least in part through apoAI, inhibits phospholipase-C activity and cytokine release in monocytes, thereby counteracting the inflammatory effect of LDL(–). HDL exerts a protective effect on endothelial cells and monocytes [8,9,10] because it inhibits cells from producing the inflammatory molecules induced by modified LDL and lipopolysaccharide (LPS). Birkelund are recipients of predoctoral fellowships from the Ministry of Education and Science (MEC) and Generalitat de Catalunya (AGAUR), respectively.
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