Ticagrelor Increases SIRT1 and HES1 mRNA Levels in Peripheral Blood Cells from Patients with Stable Coronary Artery Disease and Chronic Obstructive Pulmonary Disease

Ticagrelor is a powerful P2Y12inhibitor with pleiotropic effects in the cardiovascularsystem. Consistently, we have reported that in patients with stable coronary artery disease (CAD) andconcomitant chronic obstructive pulmonary disease (COPD) who underwent percutaneous coronaryintervention (PCI), 1-month treatment with ticagrelor was superior in improving biological markersof endothelial function, compared with clopidogrel. The objective of this study was to investigate themechanisms underlying these beneficial effects of ticagrelor by conducting molecular analyses ofRNA isolated from peripheral blood cells of these patients. We determined mRNAs levels of markersof inflammation and oxidative stress, such asRORγt(T helper 17 cells marker),FoxP3(regulatoryT cells marker),NLRP3,ICAM1,SIRT1, Notch ligandsJAG1andDLL4,andHES1, a Notch targetgene. We found that 1-month treatment with ticagrelor, but not clopidogrel, led to increased levels ofSIRT1andHES1mRNAs. In patients treated with ticagrelor or clopidogrel, we observed a negativecorrelation among changes in bothSIRT1andHES1mRNA and serum levels of Epidermal GrowthFactor (EGF), a marker of endothelial dysfunction found to be reduced by ticagrelor treatment inour previous study. In conclusion, we report that in stable CAD/COPD patients ticagrelor positivelyregulatesHES1andSIRT1, two genes playing a protective role in the context of inflammation andoxidative stress. Our observations confirm and expand previous studies showing that the beneficialeffects of ticagrelor in stable CAD/COPD patients may be, at least in part, mediated by its capacity toreduce systemic inflammation and oxidative stress