著者
Yusuke Takahara Tomotake Tokunou Toshihiro Ichiki
出版者
Japan Atherosclerosis Society
雑誌
Journal of Atherosclerosis and Thrombosis (ISSN:13403478)
巻号頁・発行日
vol.25, no.8, pp.698-708, 2018-08-01 (Released:2018-08-01)
参考文献数
38
被引用文献数
17

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.

言及状況

外部データベース (DOI)

Twitter (1 users, 1 posts, 0 favorites)

Suppression of Abdominal Aortic Aneurysm Formation in Mice by Teneligliptin, a Dipeptidyl Peptidase-4 Inhibitor https://t.co/3vyOfp3WzV 「DPP-4阻害薬のテネリグリプチンがマウスの腹部大動脈瘤形成を抑制する」 他のDPP-4iで同様の効果が出たら面白そうです。

収集済み URL リスト