Effect of myeloperoxidase modified LDL on bovine and human aortic endothelial cells

Cardiovascular disease associated with atherosclerosis is a leading cause of death worldwide. Atherosclerosis is primarily caused by the dysfunction of vascular endothelial cells and the subendothelial accumulation of oxidized forms of low-density lipoproteins (LDL). Early observations have associated fibrin deposition with atheroma plaque formation, which has led to the proposition that a decrease in endothelial cell fibrinolysis may negatively influence atherogenesis. It has been recently demonstrated that myeloperoxidase modified LDL (MoxLDL) decreases endothelial cell profibrinolytic capacity in real-time. The present study investigated the role of MoxLDL in endothelial cell dysfunction by determining the molecules that may be involved in decreasing the fibrinolysis of human aortic endothelial cells (HAEC). Accordingly, reverse transcription-quantitative PCR was performed to screen for the differential expression of major genes that are implicated in the fibrinolytic process. In addition, the response of the latter cell type to MoxLDL was compared with bovine aortic endothelial (BAE) cells. Furthermore, the effect of the treatment on the generation of reactive oxygen species (ROS) was also determined. Although the current study did not demonstrate an association between MoxLDL treatment and a change in the expression of any major fibrinolytic factor in HAEC, a discrepancy between HAEC and BAE cells with respect to their response to modified LDL treatment was observed. The result have also demonstrated that MoxLDL does not increase ROS generation in HAEC as opposed to the other major type of modified LDL, cupper oxidized LDL (CuoxLDL) that was reported to exhibit a positive effect at this level. The present study provided important insight into the different effects of MoxLDL and CuoxLDL in endothelial cells, which may aid future studies to determine the various signaling pathways that are promoted by these molecules. The results of the present study may be utilized to identify potential molecular drug targets for the treatment of atherosclerosis.