Combined Treatment of Hydroxytyrosol with Carbon Monoxide-Releasing Molecule-2 Prevents TNFα-Induced Vascular Endothelial Cell Dysfunction through NO Production with Subsequent NFκB Inactivation

الملخص EN

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 TNFα-induced cellular damage by enhancing cell survival and the suppression of caspase-3 activation.

While HT alone attenuated NFκBp65 phosphorylation and IκBα degradation triggered by TNFα in a dose-dependent manner, combined treatment of HT with CORM-2 but not iCORM-2 nearly completely blocked these TNFα effects.

Furthermore, combined action of both compounds results in the inhibition of NFκB 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 TNFα-triggered NFκBp65 and IκBα 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.