Statins inhibit oxidized-LDL-mediated LOX-1 expression, uptake of oxidized-LDL and reduction in PKB phosphorylation

Objectives: LOX-1, a lectin-like receptor on endothelial cells, facilitates the uptake of oxidized-LDL. Expression of LOX-1 is involved in the pathobiological effects of oxidized-LDL in endothelial cells, including apoptosis, suppression of cNOS activity and cell adhesion. Recent studies show that intracellular signal protein kinase B (PKB) is involved in the regulation of cNOS. Further, HMG CoA reductase inhibitors (statins) may affect LOX-1 expression. In this study, we examined the modulation of LOX-1 expression and PKB activity in response to oxidized-LDL by two different statins (simvastatin and atorvastatin). Methods and results: Cultured human coronary artery endothelial cells (HCAECs) were used in this study. Oxidized-LDL (40 mug/ml) was found to upregulate the expression of LOX-1 (mRNA and protein), enhance [I-125]-ox-LDL uptake and to reduce the phosphorylation of PKB (p-PKB), Two different statins, simvastatin and atorvastatin (each 1 and 10 muM), upregulated the activity of PKB and decreased LOX-1 expression and [125I]-ox-LDL uptake. A high concentration of statins (10 muM) gave a more potent effect than the low concentration (1 muM). The effects of the two different statins were similar. Conclusions: These observations show that statins decrease LOX-1 expression, a novel oxidized-LDL endothelial receptor, and uptake of oxidized-LDL in HCAECs. The effect of statins on LOX-1 expression is associated with ail increase in PKB activity in HCAECs. (C) 2001 Elsevier Science B.V. All rights reserved.