Ticagrelor Improves Endothelial Function by Decreasing Circulating Epidermal Growth Factor (EGF)

Ticagrelor is one of the most powerful P2Y inhibitor. We have recently reported that, in patients with concomitant Stable Coronary Artery Disease (SCAD) and Chronic Obstructive Pulmonary Disease (COPD) undergoing percutaneous coronary intervention (PCI), treatment with ticagrelor, as compared to clo...

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Published in:Frontiers in physiology 2018-04, Vol.9, p.337-337
Main Authors: Vieceli Dalla Sega, Francesco, Fortini, Francesca, Aquila, Giorgio, Pavasini, Rita, Biscaglia, Simone, Bernucci, Davide, Del Franco, Annamaria, Tonet, Elisabetta, Rizzo, Paola, Ferrari, Roberto, Campo, Gianluca
Format: Article
Language:English
Subjects:
chronic obstructive pulmonary disease (COPD)
endothelial function
eNOS
epidermal growth factor (EGF)
Physiology
stable coronary artery disease (SCAD)
ticagrelor
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Summary:Ticagrelor is one of the most powerful P2Y inhibitor. We have recently reported that, in patients with concomitant Stable Coronary Artery Disease (SCAD) and Chronic Obstructive Pulmonary Disease (COPD) undergoing percutaneous coronary intervention (PCI), treatment with ticagrelor, as compared to clopidogrel, is associated with an improvement of the endothelial function (Clinical Trial NCT02519608). In the present study, we showed that, in the same population, after 1 month treatment with ticagrelor, but not with clopidogrel, there is a decrease of the circulating levels of epidermal growth factor (EGF) and that these changes in circulating levels of EGF correlate with on-treatment platelet reactivity. Furthermore, in human umbilical vein endothelial cells (HUVEC) incubated with sera of the patients treated with ticagrelor, but not with clopidogrel there is an increase of p-eNOS levels. Finally, analyzing the changes in EGF and p-eNOS levels after treatment, we observed an inverse correlation between p-eNOS and EGF changes only in the ticagrelor group. Causality between EGF and eNOS activation was assessed in HUVEC where we showed that EGF decreases eNOS activity in a dose dependent manner. Taken together our data indicate that ticagrelor improves endothelial function by lowering circulating EGF that results in the activation of eNOS in the vascular endothelium.
ISSN:1664-042X
1664-042X
DOI:10.3389/fphys.2018.00337