Combined Treatment of Hydroxytyrosol with Carbon Monoxide-Releasing Molecule-2 Prevents TNFα-Induced Vascular Endothelial Cell Dysfunction through NO Production with Subsequent NFκB Inactivation. (27th August 2013)

• Record Type: Journal Article
• Authors: Zrelli, Houda; Wei Wu, Che; Zghonda, Nahla; Shimizu, Hidehisa; Miyazaki, Hitoshi
• Other Names: Yard Benito A. Academic Editor.
• Is Part Of: BioMed research international. Volume 2013(2013)
• Publication Date: 2013-08-27
• Subjects: Medicine -- Periodicals; Biology -- Periodicals; Biotechnology -- Periodicals; Life sciences -- Periodicals; 610.5
• DOI: 10.1155/2013/912431
• Languages: English
• ISSNs: 2314-6133

Abstract

Abstract : This study investigated the atheroprotective properties of olive oil polyphenol, hydroxytyrosol (HT), in combination with carbon monoxide-releasing molecule-2 (CORM-2) that acts as a carbon monoxide donor using vascular endothelial cells (VECs). Our results showed that CORM-2 could strengthen the cytoprotective and anti-apoptotic effects of HT against TNF α -induced cellular damage by enhancing cell survival and the suppression of caspase-3 activation. While HT alone attenuated NF κ Bp65 phosphorylation and I κ B α degradation triggered by TNF α in a dose-dependent manner, combined treatment of HT with CORM-2 but not iCORM-2 nearly completely blocked these TNF α effects. Furthermore, combined action of both compounds results in the inhibition of NF κ B nuclear translocation. Results also indicate that both compounds time-dependently increased eNOS phosphorylation levels and the combination of HT with CORM-2 was more effective in enhancing eNOS activation and NO production in VECs. The NOS inhibitor, L-NMMA, significantly suppressed the combined effects of HT and CORM-2 on TNF α -triggered NF κ Bp65 and I κ B α phosphorylation as well as decreased cell viability. Together, these data suggest that carbon monoxide-dependent regulation of NO production by the combination of HT with CORM-2 may provide a therapeutic benefit in the treatment of endothelial dysfunction and atherosclerosis.