ticagrelor and empagliflozin

In the current investigation, the effects of the P2Y12 blocker ticagrelor, the sodium/glucose transporter-2-inhibitor empagliflozin, and the selective estrogen receptor modulator tamoxifen were examined against rheumatoid arthritis (RA)/diabetes mellitus (DM)-co-morbidity-induced defects in vascular reactivity.. After model setting, rats were allocated into a normal control, an RA/DM-co-morbidity, and three treatment groups receiving ticagrelor, empagliflozin and tamoxifen. Aorta tissue was isolated for enzyme-linked immunosorbent assay (ELISA) and western blot estimation of the pro-inflammatory molecules angiotensin-II (Ang-II) and endothelin-1 (ET-1), the adhesion molecules P-selectin and vascular cell adhesion molecule-1 (VCAM-1), the energy preserving molecule adenosine-5'-monophosphate-activated protein kinase (AMPK), and the anti-inflammatory molecule vasoactive intestinal peptide (VIP). Estimations of endothelial nitric oxide synthase (eNOS) and matrix metalloproteinase (MMP)-2 were performed immunohistochemically, together with histopathological examination using hematoxylin and eosin and Masson trichrome staining. An in vitro study on rat aortic strips was conducted to assess aorta vasorelaxation.. Ticagrelor, empagliflozin and tamoxifen significantly increased aorta tissue AMPK and eNOS and decreased Ang-II, ET-1, P-selectin, VCAM-1 and VIP levels compared with RA/DM-co-morbidity, coupled with improved acetylcholine vasorelaxation in vitro.. Ticagrelor, empagliflozin and tamoxifen may correct vascular reactivity defects, where modulation of vascular AMPK, eNOS, Ang-II, ET-1, P-selectin, VCAM-1 and MMP-2 underline their protective effects.

Topics: AMP-Activated Protein Kinase Kinases; Angiotensin II; Animals; Aorta; Arthritis, Rheumatoid; Benzhydryl Compounds; Diabetes Mellitus, Experimental; Endothelium, Vascular; Female; Glucosides; Nitric Oxide; Nitric Oxide Synthase Type III; Protein Kinases; Purinergic P2 Receptor Antagonists; Rats; Rats, Inbred WF; Receptors, Purinergic P2Y12; Selective Estrogen Receptor Modulators; Sodium-Glucose Transporter 2 Inhibitors; Tamoxifen; Ticagrelor; Vascular Cell Adhesion Molecule-1; Vasodilation