抄録
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.
| 元の言語 | 英語 |
|---|---|
| ページ（範囲） | 698-708 |
| ページ数 | 11 |
| ジャーナル | Journal of atherosclerosis and thrombosis |
| 巻 | 25 |
| 発行部数 | 8 |
| DOI | |
| 出版物ステータス | 出版済み - 1 1 2018 |
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All Science Journal Classification (ASJC) codes
- Internal Medicine
- Cardiology and Cardiovascular Medicine
- Biochemistry, medical
これを引用
Suppression of abdominal aortic aneurysm formation in mice by teneligliptin, a dipeptidyl peptidase-4 inhibitor. / Takahara, Yusuke; Tokunou, Tomotake; Ichiki, Toshihiro.
：: Journal of atherosclerosis and thrombosis, 巻 25, 番号 8, 01.01.2018, p. 698-708.研究成果: ジャーナルへの寄稿 › 記事
}
TY - JOUR
T1 - Suppression of abdominal aortic aneurysm formation in mice by teneligliptin, a dipeptidyl peptidase-4 inhibitor
AU - Takahara, Yusuke
AU - Tokunou, Tomotake
AU - Ichiki, Toshihiro
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85051135142&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85051135142&partnerID=8YFLogxK
U2 - 10.5551/jat.42481
DO - 10.5551/jat.42481
M3 - Article
C2 - 29321388
AN - SCOPUS:85051135142
VL - 25
SP - 698
EP - 708
JO - Journal of Atherosclerosis and Thrombosis
JF - Journal of Atherosclerosis and Thrombosis
SN - 1340-3478
IS - 8
ER -