Dipeptidyl-peptidase-4 inhibitor,alogliptin,attenuates arterial inflammation and neointimal formation after injury in low-density lipoprotein (LDL) receptor-deficient mice

Background: the results of recent studies suggest that dipeptidyl-peptidase-4 inhibitors have antiatherogenic effects. however,whether or not dipeptidyl-peptidase-4 inhibitors could suppress arterial inflammation and intimal hyperplasia after injury remains undetermined. the present study aims to clarify the anti-inflammatory effects of the dipeptidyl-peptidase-4 inhibitor,alogliptin (agp),on the arteries of atherogenic low-density lipoprotein receptor-deficient (lko) mice.methods and results: we compared intimal hyperplasia in lko mice 2 weeks after femoral artery injury using an external vascular cuff model. all mice received oral injection of agp (20 mg/kg per day) or normal saline (control) once daily for 14 days. fasting blood sugar levels,serum cholesterol levels,or blood pressure did not significantly differ between the 2 groups. plasma levels of active glucagon-like peptide-1 were higher in the agp than in the control lko mice (22.2±1.9 versus 15.6±0.9 pg/ml; p<0.05). compared with saline,agp significantly reduced intimal hyperplasia (1087±127 versus 1896±140 μm(2); p<0.001) as well as the intima/media ratio (0.08±0.01 versus 0.16±0.02; p<0.001). immunostaining showed that agp reduced proliferating cells (proliferating cell nuclear antigen-positive nuclei; p<0.001),percent smooth-muscle cell area (α-sma-positive cells; p<0.001),inflammatory cells infiltration (lymphocyte antigen 6 complex-positive cells; p<0.05),tumor necrosis factor-α expression (p<0.05),and percent phospho-nf-κb-positive cell compared with saline. levels of tumor necrosis factor -α (0.5-fold p<0.05),monocyte chemoattractant protein 1 (0.3-fold p<0.01),and interleukin-1β (0.2-fold p<0.05) mrna were lower in the injured arteries of the agp than in the control group.conclusions: agp appeared to suppress neointimal formation by inhibiting inflammation,independently of its effects on glucose or cholesterol metabolism in atherogenic lko mice. © 2015 the authors. published on behalf of the american heart association,inc.,by wiley blackwell.