A dipeptidyl peptidase-4 inhibitor but not incretins suppresses abdominal aortic aneurysms in angiotensin II-infused apolipoprotein E-null mice

Aim: the main pathophysiology of abdominal aortic aneurysm (aaa) considerably overlaps with that of atherosclerosis. we reported that incretins [glucagon-like peptide (glp)-1 and glucose-dependent insulinotropic polypeptide (gip)] or a dipeptidyl peptidase-4 inhibitor (dpp-4i) suppressed atherosclerosis in apolipoprotein e-null (apoe－/－) mice. here we investigated the effects of incretin-related agents on aaa in a mouse model. methods: apoe－/－ mice maintained on an atherogenic diet were subcutaneously infused with saline,ang ii (2000 ng/kg/min),ang ii,and native glp-1 (2.16 nmol/kg/day) or ang ii and native gip (25 nmol/kg/day) for 4 weeks. dpp-4i (mk0626,6 mg/kg/day) was provided in the diet to the ang ii-infused mice with or without incretin receptor antagonists [(pro3) gip and exendin (9-39)]. results: aaa occurred in 70% of the animals receiving ang ii. dpp-4i reduced this rate to 40% and significantly suppressed aaa dilatation,fibrosis,and thrombosis. in contrast,incretins failed to attenuate aaa. incretin receptor blockers did not reverse the suppressive effects of dpp-4i on aaa. in the aorta,dpp-4i significantly reduced the expression of interleukin-1β and increased that of tissue inhibitor of metalloproteinase (timp)-2. in addition,dpp-4i increased the ratio of timp-2 to matrix metalloproteinases-9. conclusions: dpp-4i,mk0626,but not native incretins has protective effects against aaa in ang ii-infused apoe－/－ mice via suppression of inflammation,proteolysis,and fibrosis in the aortic wall. © 2016,journal of atherosclerosis and thrombosis. all rights reserved.