Suppression of Abdominal Aortic Aneurysm Formation in Mice by Teneligliptin, a Dipeptidyl Peptidase-4 Inhibitor

Access this Article

Search this Article

Author(s)

    • Takahara Yusuke
    • Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Kyushu University
    • Tokunou Tomotake
    • Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Kyushu University|Center for Disruptive Cardiovascular Medicine, Department of Advanced Cardiovascular Regulation and Therapeutics, Kyushu University
    • Ichiki Toshihiro
    • Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Kyushu University|Department of Cardiology, Harasanshin Hospital

Abstract

<p><b>Aim:</b> 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.</p><p><b>Methods:</b> 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.</p><p><b>Results:</b> Treatment with teneligliptin significantly reduced the AAA formation rate (30.7% vs. 71.4% vs. control, <i>P</i><0.05), aortic dilatation (1.32±0.09 mm vs. 1.76±0.18 mm in the control, <i>P</i><0.05) and severity score (0.75±0.28 vs. 1.91±0.4 in the control, <i>P</i><0.05). Elastin degradation grade was also attenuated in DPP-4i group (2.83±0.17 vs. 3.45±0.16 in the control, <i>P</i><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, <i>P</i><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.</p><p><b>Conclusion:</b> 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.</p>

Journal

  • Journal of Atherosclerosis and Thrombosis

    Journal of Atherosclerosis and Thrombosis 25(8), 698-708, 2018

    Japan Atherosclerosis Society

Codes

  • NII Article ID (NAID)
    130007429758
  • Text Lang
    ENG
  • ISSN
    1340-3478
  • Data Source
    J-STAGE 
Page Top