Dipeptidyl peptidase-4 inhibitor linagliptin attenuates neointima formation after vascular injury

Cardiovascular Diabetology

Toshihiko Yanase¹  Makito Tanabe¹  Ryoko Nagaishi¹  Kunitaka Murase¹  Tomoko Tanaka¹  Hiroyuki Takahashi¹  Yuriko Hamaguchi¹  Takako Kawanami¹  Takashi Nomiyama¹  Yuichi Terawaki¹ 

[1] Department of Endocrinology and Diabetes Mellitus, School of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku 814-0180, Fukuoka, Japan

关键词: VSMC proliferation;    Neointima formation;    Linagliptin;    DPP-4 inhibitor;   

Others  :  1118935
DOI  :  10.1186/s12933-014-0154-3

 received in 2014-09-03, accepted in 2014-10-30,  发布年份 2014

【 摘 要 】

Background

Recently, glucagon-like peptide-1 (GLP-1)-based therapy, including dipeptidyl peptidase-4 (DPP-4) inhibitors and GLP-1 receptor agonists, has emerged as one of the most popular anti-diabetic therapies. Furthermore, GLP-1-based therapy has attracted increased attention not only for its glucose-lowering ability, but also for its potential as a tissue-protective therapy. In this study, we investigated the vascular-protective effect of the DPP-4 inhibitor, linagliptin, using vascular smooth muscle cells (VSMCs).

Methods

Six-week-old male C57BL/6 mice were divided into control (n =19) and linagliptin (3 mg/kg/day, n =20) treated groups. Endothelial denudation injuries were induced in the femoral artery at 8 weeks of age, followed by evaluation of neointima formation at 12 weeks. To evaluate cell proliferation of rat aortic smooth muscle cells, a bromodeoxyuridine (BrdU) incorporation assay was performed.

Results

Linagliptin treatment reduced vascular injury-induced neointima formation, compared with controls (p <0.05). In these non-diabetic mice, the body weight and blood glucose levels did not change after treatment with linagliptin. Linagliptin caused an approximately 1.5-fold increase in serum active GLP-1 concentration, compared with controls. In addition, the vascular injury-induced increase in the oxidative stress marker, urinary 8-OHdG, was attenuated by linagliptin treatment, though this attenuation was not statistically significant (p =0.064). Moreover, linagliptin did not change the serum stromal cell-derived factor-1α (SDF-1α) or the serum platelet-derived growth factor (PDGF) concentration. However, linagliptin significantly reduced in vitro VSMC proliferation.

Conclusion

Linagliptin attenuates neointima formation after vascular injury and VSMC proliferation beyond the glucose-lowering effect.

【 授权许可】

   
2014 Terawaki et al.; licensee BioMed Central Ltd.

【 图 表 】

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