Combinational Therapy with Aspirin and Ticagrelor Alleviates Vascular Inflammation and Angiotensin IIdriven Abdominal Aortic Aneurysm Formation in Mice

Abstract

Background: Abdominal aortic aneurysm (AAA) is a severe form of blood vessel-related disease. Medial degeneration and inflammation are typical characteristic of AAA. Activated platelets release many pro-inflammatory cytokines and participate in the initial inflammatory response to various vascular diseases. Although there are some studies on the effects of APAs on AAA, it is yet unknown whether the new P2Y12 receptor inhibitor ticagrelor (T) can inhibit AAA. Herein, we explored the consequences of ticagrelor exposure on AAA progression and determined whether a combinational therapy, involving T and aspirin (A), exerts a stronger inhibitory effect in vivo. Methods: AAA was established in apolipoprotein E-deficient (ApoE-/- ) mice via a 28-day administration of angiotensin II (Ang II). Next, the mice were arbitrarily separated into 5 groups: saline infusion alone (sham), Ang II infusion alone, Ang II infusion plus oral A (10 mg•kg-1•d-1), Ang II infusion plus oral T (120 mg.kg-1.d-1), Ang II infusion plus combinational therapy with A (10 mg•kg-1•d-1) and T (120 mg.kg-1.d-1). Results: The combined treatment markedly suppressed the Ang II-driven elevation of maximal aortic diameter, aneurysm formation (26.7% decrease, P<0.05), alterations in aortic expansion, elastic lamina destruction, platelet deposition, and inflammatory cytokine accumulation. In addition, it also diminished matrix metalloproteinase (MMP)-2 and MMP-9 production. Conclusions: A combinational therapy of A and T, but not individual drugs, inhibits Ang II-driven AAA generation in mice in vivo, and this process may be regulated by a suppressed inflammatory response.