Oxidized low-density lipoproteins (oxLDL) exhibit proinflammatory properties and play a role in @entity731 plaque formation, @entity397 , and subsequent @entity715 . OxLDL alter the activity of the transcription factor NF-kappaB that is involved in the expression of immune and inflammatory genes. In contrast, high-density lipoproteins (HDL) are anti-atherogenic and exhibit anti-inflammatory properties. This work aimed to investigate how oxLDL activate NF-kappaB and whether and how HDL may prevent NF-kappaB activation. In cultured @entity95 smooth muscle cells, mitogenic concentrations of mildly oxLDL trigger a rapid and transient NF-kappaB activation, which is strongly inhibited by HDL. Growth factors, @entity4357 3-kinase/Akt, and @entity5597 kinase pathways are not implicated in the oxLDL-induced NF-kappaB activation and are not targets of HDL. OxLDL induce reactive @entity26 species (ROS) generation and proteasome activation, which are implicated in NF-kappaB activation, as suggested by the inhibitory effect of the antioxidants @entity898 and @entity13373 and the proteasome inhibitor PSI. HDL were able to prevent the intracellular ROS rise triggered by oxLDL or @entity274 , thereby inhibiting the subsequent proteasome activation, IkappaB degradation, and NF-kappaB activation. In conclusion, the oxLDL-induced NF-kappaB activation involves ROS generation and proteasome activation, both events being inhibited by HDL. This 'antioxidant' and potentially anti-inflammatory effect of HDL may participate in their general anti-atherogenic properties.

HDL counterbalance the proinflammatory effect of oxidized LDL by inhibiting intracellular reactive XXXX species rise, proteasome activation, and subsequent NF-kappaB activation in smooth muscle cells.

@entity274 :: ('CHEBI:16240', 'Chemical') :: ['H2O2'] @entity4357 :: ('MESH:D010716', 'Chemical') :: ['phosphatidylinositol'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity95 :: ('9986', 'Species') :: ['rabbit'] @entity898 :: ('MESH:D000111', 'Chemical') :: ['N-acetyl-L-cysteine'] @entity13373 :: ('MESH:C020972', 'Chemical') :: ['pyrrolidinedithiocarbamate'] @entity5597 :: ('MESH:D013110', 'Chemical') :: ['sphingosine'] @entity397 :: ('MESH:D012421', 'Disease') :: ['rupture'] @entity731 :: ('MESH:D050197', 'Disease') :: ['atherosclerosis'] @entity715 :: ('MESH:D013927', 'Disease') :: ['thrombosis']
@entity26 :: (MESH:D010100,Chemical) :: ['oxygen']
