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

International Journal of Molecular Sciences

Paola Rizzo¹  Fernanda Martini¹  Luisa Marracino¹  Anna Piredda²  Alessandra Scoccia²  LauraSofia Cardelli²  Valeria Martino²  Francesca Fortini³  Giorgio Aquila³  Rita Pavasini⁴  Antonio Pannuti⁴  Marco Manfrini⁴  Roberto Ferrari⁵  Ilaria Bononi⁵  Francesco Vieceli Dalla Sega⁵  Gianluca Campo⁶ 

[1] Research, 48033 Cotignola, Italy;Cardiovascular Institute, Azienda Ospedaliero-Universitaria di Ferrara, 44124 Cona, Italy;Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy;Department of Morphology, Surgery and Experimental Medicine and Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 44121 Ferrara, Italy;;Maria Cecilia Hospital, GVM Care &University of Hawaii Cancer Center, University of Hawaii, Honolulu, HI 96813, USA;

关键词: coronary artery disease (cad);    chronic obstructive pulmonary disease (copd);    ticagrelor;    clopidogrel;    notch signaling;    sirt1;   

DOI  :  10.3390/ijms21051576

来源: DOAJ

【 摘 要 】

Ticagrelor is a powerful P2Y₁₂ inhibitor with pleiotropic effects in the cardiovascular system. Consistently, we have reported that in patients with stable coronary artery disease (CAD) and concomitant chronic obstructive pulmonary disease (COPD) who underwent percutaneous coronary intervention (PCI), 1-month treatment with ticagrelor was superior in improving biological markers of endothelial function, compared with clopidogrel. The objective of this study was to investigate the mechanisms underlying these beneficial effects of ticagrelor by conducting molecular analyses of RNA isolated from peripheral blood cells of these patients. We determined mRNAs levels of markers of inflammation and oxidative stress, such as RORγt (T helper 17 cells marker), FoxP3 (regulatory T cells marker), NLRP3, ICAM1, SIRT1, Notch ligands JAG1 and DLL4, and HES1, a Notch target gene. We found that 1-month treatment with ticagrelor, but not clopidogrel, led to increased levels of SIRT1 and HES1 mRNAs. In patients treated with ticagrelor or clopidogrel, we observed a negative correlation among changes in both SIRT1 and HES1 mRNA and serum levels of Epidermal Growth Factor (EGF), a marker of endothelial dysfunction found to be reduced by ticagrelor treatment in our previous study. In conclusion, we report that in stable CAD/COPD patients ticagrelor positively regulates HES1 and SIRT1, two genes playing a protective role in the context of inflammation and oxidative stress. Our observations confirm and expand previous studies showing that the beneficial effects of ticagrelor in stable CAD/COPD patients may be, at least in part, mediated by its capacity to reduce systemic inflammation and oxidative stress.

【 授权许可】

Unknown