© 2001 by European Society of Cardiology
Copyright © 2001, European Society of Cardiology
Statins inhibit oxidized-LDL-mediated LOX-1 expression, uptake of oxidized-LDL and reduction in PKB phosphorylation
Departments of Medicine and Physiology, University of Arkansas for Medical Sciences and Central Arkansas Veterans Health Care System, Little Rock, AR, USA
* Corresponding author. Division of Cardiovascular Medicine, University of Arkansas for Medical Sciences, 4301 West Markham St., Mail Slot 532, Little Rock, AR 72205-7199, USA. Tel.: +1-501-296-1401; fax: +1-501-686-6180 mehtajl{at}uams.edu
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 µg/ml) was found to upregulate the expression of LOX-1 (mRNA and protein), enhance [125I]-ox-LDL uptake and to reduce the phosphorylation of PKB (p-PKB). Two different statins, simvastatin and atorvastatin (each 1 and 10 µM), upregulated the activity of PKB and decreased LOX-1 expression and [125I]-ox-LDL uptake. A high concentration of statins (10 µM) gave a more potent effect than the low concentration (1 µM). 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 an increase in PKB activity in HCAECs.
KEYWORDS Endothelial function; Lipoproteins; Protein kinases; Statins
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