Abstract

Aim: Dipeptidyl peptidase-4 (DPP-4) inhibitors lower blood glucose levels through inhibition of incretin degradation, which stimulates insulin secretion. Recent studies reported that DPP-4 inhibitors suppressed atherogenesis in apolipoprotein E-knockout (ApoEKO) mice. In this study, we investigated whether teneligliptin, a DPP-4 inhibitor, affects the development of abdominal aortic aneurysms (AAA) in ApoEKO mice.Methods: ApoEKO mice were fed a high-fat diet (HFD) and infused with angiotensin (Ang) II by osmotic mini pumps for 4 weeks to induce AAA with (DPP-4i group) or without (control group) teneligliptin administered orally from 1 week before HFD and Ang II infusion to the end of the experiment. Confluent rat vascular smooth muscle cells (VSMCs) were serum-starved for 48 hours, then incubated with or without teneligliptin for another 24 hours and stimulated with Ang II.Results: Treatment with teneligliptin significantly reduced the AAA formation rate (30.7% vs. 71.4% vs. control, P < 0.05), aortic dilatation (1.32 ± 0.09 mm vs. 1.76 ± 0.18 mm in the control, P < 0.05) and severity score (0.75 ± 0.28 vs. 1.91 ± 0.4 in the control, P < 0.05). Elastin degradation grade was also attenuated in DPP-4i group (2.83 ± 0.17 vs. 3.45 ± 0.16 in the control, P < 0.05). The number of macrophages infiltrating into the abdominal aorta was decreased in the DPP-4i group (51.8 ± 29.8/section vs. 219.5 ± 78.5/section in the control, P < 0.05). Teneligliptin attenuated Ang II-induced phosphorylation of extracellular signal-regulated kinase (ERK) and Akt, and mRNA expression of monocyte chemoattractant protein-1 in VSMCs.Conclusion: Treatment with teneligliptin suppressed AAA formation in ApoEKO mice with HFD and Ang II infusion. Suppression of macrophage infiltration by teneligliptin may be involved in the inhibition of AAA formation.

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