The effect of anagliptin on intimal hyperplasia of rat carotid artery after balloon injury

Abstract

The present study evaluated the effect of anagliptin on intimal hyperplasia following carotid artery injury in Sprague‑Dawley rats. Sprague‑Dawley rats weighing 280‑300 g were injured using a 2F Fogarty balloon embolectomy catheter. The rats were divided into injury‑(saline) and anagliptin‑(10 mg/kg/day) treated groups. vascular injuries were induced in the left carotid artery, followed by evaluation of neointima formation at 28 days. The right and left carotid arteries were harvested and evaluated with histological evaluation, and the plasma activity of glucagon‑like peptide 1 receptor (GLP‑1), stromal cell‑derived factor (SDF)‑1α, interleukin (IL)‑6, IL‑1β and tumor necrosis factor (TNF)‑α were detected by ELISA analysis. Treatment with anagliptin decreased balloon injury‑induced neointima formation, compared with the injury group (P<0.01). Body weight and food consumption did not alter following treatment with anagliptin. Anagliptin caused an increase in the serum active GLP‑1 concentration, compared with the injury group. In addition, serum SDF‑1α was significantly decreased by treatment with anagliptin (P<0.001). Anagliptin altered the serum activity of IL‑6, IL‑1β and TNF‑α (P<0.01). The results of the present study demonstrated that anagliptin appeared to attenuate neointimal formation by inhibiting inflammatory cytokines and chemokines following balloon injury, and that treatment with a dipeptidyl peptidase 4 inhibitor may be useful for future preclinical studies and potentially for the inhibition of thrombosis formation following percutaneous coronary intervention.

Figure 1.

Neointimal hyperplasia formation following balloon injury. (A) Tissues were evaluated by hematoxylin and eosin staining (magnification, ×200) at 28 days subsequent to balloon injury. The (B) ratio of intima/media (normalized to the uninjured tissue), (C) area of the intima and (D) area of the media were calculated and between the right and left carotid artery in the balloon injury group. Data are presented as the mean ± standard error of the mean.

Figure 2.

Anagliptin attenuates neointimal hyperplasia following balloon injury. (A) Tissues were evaluated by hematoxylin and eosin staining (magnification, ×200) at 28 days following the commencement of treatment with anagliptin. (B) The intima/media ratio (normalized to injury), and the area of the intima and media were calculated in the injury and anagliptin groups. (C) Histological sections of injured and anagliptin-treated arteries were stained with elastic van Gieson (magnification, ×200). **P<0.01 vs. injury. Data are presented as the mean ± standard error of the mean. Ana, anagliptin.

Figure 3.

Comparison of the differences in (A) body weight and (B) food consumption in the injury group and the anagliptin-treated group. Data are presented as the mean ± standard error of the mean. Ana, anagliptin.

Figure 4.

Measurement of the serum concentration of GLP-1 and SDF-1α following treatment with anagliptin. (A) The serum concentration of GLP-1 in the injury and anagliptin groups. (B) Serum level of SDF-1α in the injury and Anagliptin groups. ***P<0.001 vs. Injury + vehicle group. Data are presented as the mean ± standard error of the mean. Ana, anagliptin; GLP-1, glucagon-like peptide 1 receptor; SDF-1α, stromal cell-derived factor 1α.

Figure 5.

Measurement of the serum activity of inflammatory cytokines following treatment with anagliptin. At 7 days post-injury, anagliptin decreased the serum activity of (A) IL-6, (B) IL-1β and (C) TNF-α. **P<0.01 vs. injury group. Data are presented as the mean ± standard error of the mean obtained from five independent experiments. Ana, anagliptin; IL, interleukin; TNF-α, tumor necrosis factor.