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Dehydroepiandrosterone Delays LDL Oxidation In Vitro and Attenuates Several oxLDL-Induced Inflammatory Responses in Endothelial Cells

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Dehydroepiandrosterone (DHEA) has a protective role against atherosclerosis, most likely mediating an antiinflammatory action. In order to understand the mechanisms involved in this protection, we evaluated the effects of DHEA on several molecules involved in the inflammatory response. Reactive oxygen species (ROS), expression of adhesion molecules, activation of the NF-κB/IκB-α pathway and of the AP-1 transcription factor were evaluated in human umbilical vein endothelial cells (HUVECs) treated with oxidized low density lipoproteins (oxLDL) and DHEA. We also determined if DHEA affected LDL oxidation in vitro. 100 μM DHEA-treatment inhibited the oxLDL-induced expression of ICAM-1, VCAM-1, PECAM-1, ROS production, and U937 cells adhesion to HUVECs. DHEA also delayed the kinetics of LDL oxidation in vitro. While DHEA did not affect the translocation of NF-κB neither the degradation IκB-α, it led to an increased translocation of AP-1. Our results suggest that DHEA inhibits the expression of molecules involved in the inflammatory process in endothelial cells activated with oxLDL, therefore its potential anti-inflammatory properties should be evaluated for the treatment of chronic inflammatory diseases such as atherosclerosis.





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Keywords: AP-1; DHEA; LDL; NF-κB; ROS; cell adhesion; endothelial cells; inflammation

Document Type: Research Article

Publication date: September 1, 2007

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  • Inflammation & Allergy - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in inflammation and allergy e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in inflammation and allergy. As the discovery, identification, characterization and validation of novel human drug targets for anti-inflammation and allergy drug discovery continues to grow, this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.
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