Effects of differently oxidized LDL on the expression of pro-inflammatory molecules in human monocytes in vitro.

The oxidation of low-density lipoprotein (LDL) is thought to be a major contributor to the development of atherosclerosis and considerable evidence has accumulated showing that oxidized LDL (ox LDL) induces cell damage and pro-atherogenic events. However, evidence that oxidized LDL directly causes atherosclerosis is lacking. We studied whether native and enzymatically or chemically ox LDL at concentrations of 5 and 100 μg/mL is cytotoxic to or promotes pro-atherogenic activation of human primary monocytes in culture. Both types of ox LDL (100 μg/mL), but not native LDL added to monocytes for 24 h significantly diminish DNA synthesis and increase cell death. In addition, both preparations of ox LDL inhibit cytokine and metalloproteinase production, diminish cellular oxygen consumption and induce PPARγ expression. Enzymatically ox LDL, but not LDL oxidized by copper sulfate, also increases the monocyte metabolic rate and induces intracellular lipid accumulation. Low concentrations of either preparation of o...