Suppression of Abdominal Aortic Aneurysm Formation in Mice by Teneligliptin, a Dipeptidyl Peptidase-4 Inhibitor.
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.
['Takahara|Yusuke|Y|', 'Tokunou|Tomotake|T|', 'Ichiki|Toshihiro|T|']
D000818:Animals D017544:Aortic Aneurysm, Abdominal D002478:Cells, Cultured D054873:Dipeptidyl-Peptidase IV Inhibitors D004195:Disease Models, Animal D008264:Macrophages D008297:Male D051379:Mice D000074085:Mice, Knockout, ApoE D011720:Pyrazoles D053778:Thiazolidines
Abdominal aortic aneurysm Dipeptidyl peptidase-4 inhibitor ERK Angiotensin II