Elucidating the Effect of HDL on the OxPAPC Response in Human Endothelial Cells

Abstract

Atherosclerosis is a chronic inflammatory disorder and the primary cause of cardiovascular diseases. Oxidized 1‐palmitoyl‐2‐ arachidonyl‐sn‐phosphatidylcholine (OxPAPC) accumulates in atherosclerotic lesions and alters the expression of over 1000 genes in human aortic endothelial cells (HAECs). High‐density lipoprotein (HDL) has been shown to suppress the effects of OxPAPC, thereby protecting the cell from oxidative stress and inflammation. In this study, we used microarray analysis in 5 HAEC donors, to demonstrate that HDL reduces the transcriptional response of up to 65% of the genes regulated by OxPAPC. We define this effect as the HDL response. Due to the variation in the OxPAPC and HDL responses among the donors, we did not identify specific pathways affected by HDL. Still, we investigated both receptor specific and receptor independent mechanisms mediating the HDL response. Using siRNA mediated gene knockdown, we determined that the HDL response is independent of the expression of scavenger receptor class B‐1. We further demonstrate that cholesterol loading of the cell membrane is able to mimic some but not all of the action of HDL. Taken together, our work provides greater insight into the mechanism by which HDL regulates endothelial cell function.