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A Dipeptidyl Peptidase-4 Inhibitor but not Incretins Suppresses Abdominal Aortic Aneurysms in Angiotensin II-Infused Apolipoprotein E-Null Mice
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- Kohashi Kyoko
- Department of Medicine, Division of Diabetes, Metabolism, and Endocrinology, Showa University School of Medicine
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- Hiromura Munenori
- Department of Medicine, Division of Diabetes, Metabolism, and Endocrinology, Showa University School of Medicine
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- Mori Yusaku
- Department of Medicine, Division of Diabetes, Metabolism, and Endocrinology, Showa University School of Medicine
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- Terasaki Michishige
- Department of Medicine, Division of Diabetes, Metabolism, and Endocrinology, Showa University School of Medicine
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- Watanabe Takuya
- Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences
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- Kushima Hideki
- Department of Medicine, Division of Diabetes, Metabolism, and Endocrinology, Showa University School of Medicine
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- Shinmura Kyoko
- Department of Medicine, Division of Diabetes, Metabolism, and Endocrinology, Showa University School of Medicine
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- Tomoyasu Masako
- Department of Medicine, Division of Diabetes, Metabolism, and Endocrinology, Showa University School of Medicine
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- Nagashima Masaharu
- Department of Medicine, Division of Diabetes, Metabolism, and Endocrinology, Showa University School of Medicine Hamano Nagashima Clinic
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- Hirano Tsutomu
- Department of Medicine, Division of Diabetes, Metabolism, and Endocrinology, Showa University School of Medicine
Bibliographic Information
- Other Title
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- A dipeptidyl peptidase-4 inhibitor but not incretins suppreses abdominal aortic aneurysms in angiotensin II-infused apolipoprotein E-null mice
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Description
Aim: The main pathophysiology of abdominal aortic aneurysm (AAA) considerably overlaps with that of atherosclerosis. We reported that incretins [glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP)] or a dipeptidyl peptidase-4 inhibitor (DPP-4I) suppressed atherosclerosis in apolipoprotein E-null (Apoe－/－) mice. Here we investigated the effects of incretin-related agents on AAA in a mouse model.<br>Methods: Apoe－/－ mice maintained on an atherogenic diet were subcutaneously infused with saline, Ang II (2000 ng/kg/min), Ang II, and native GLP-1 (2.16 nmol/kg/day) or Ang II and native GIP (25 nmol/kg/day) for 4 weeks. DPP-4I (MK0626, 6 mg/kg/day) was provided in the diet to the Ang II-infused mice with or without incretin receptor antagonists [(Pro3) GIP and exendin (9-39)].<br>Results: AAA occurred in 70% of the animals receiving Ang II. DPP-4I reduced this rate to 40% and significantly suppressed AAA dilatation, fibrosis, and thrombosis. In contrast, incretins failed to attenuate AAA. Incretin receptor blockers did not reverse the suppressive effects of DPP-4I on AAA. In the aorta, DPP-4I significantly reduced the expression of Interleukin-1β and increased that of tissue inhibitor of metalloproteinase (TIMP)-2. In addition, DPP-4I increased the ratio of TIMP-2 to matrix metalloproteinases-9.<br>Conclusions: DPP-4I, MK0626, but not native incretins has protective effects against AAA in Ang II-infused Apoe－/－ mice via suppression of inflammation, proteolysis, and fibrosis in the aortic wall.
Journal
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- Journal of Atherosclerosis and Thrombosis
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Journal of Atherosclerosis and Thrombosis 23 (4), 441-454, 2016
Japan Atherosclerosis Society
