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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.00142

Vildagliptin reduces stenosis of injured carotid artery in diabetic mouse through inhibiting vascular smooth muscle cell proliferation via ER stress/NF-κB pathway

  • 1Nanjing Medical University, China
  • 2First Affiliated Hospital, Nanjing Medical University, China
  • 3Second Affiliated Hospital of Southeast University, China
  • 4Huai'an Second People's Hospital, China

Dipeptidyl peptidase-4 (DPP-4) inhibitors are novel anti-hyperglycemic drugs for type 2 diabetes. It has been reported that DDP-4 inhibitor could exert pleiotropic effects on cardiovascular system. This study was to explore the effect and mechanism of vildagliptin on the stenosis of injured carotid artery in diabetic mouse. Twenty six-week-old male db/db mice (BKS) were randomized into vildagliptin treated and vehicle control groups. Ligation injury was first performed in left carotid arteries of all diabetic mice, then oral vildagliptin or equal amount of PBS was correspondingly administered to the mice from the next day to ligation injury for 4 weeks. Effects on proliferation were detected via histological and morphometric analysis. Endoplasmic reticulum (ER) stress and nuclear factor kappa B (NF-κB) markers were determined by immunoblot analysis. After 4 weeks of vildagliptin delivery, it was observed that the intimal area and neointimal thickness of the ligated carotid arteries were significantly reduced as compared to the control group. In vivo, vildagliptin suppressed the expressions of PCNA and α-SMA, phospho-p65, phospho-IKKα/β, GRP78 and CHOP, as well as IRE-1 in vascular smooth muscle cells (VSMCs). In vitro, the proliferation and hypertrophy of VSMCs were significantly inhibited by blocking the IRE-1 pathway, and the inhibition of phospho-IRE-1 expression down-regulated the expression of phospho-IKKα/β in VSMCs. Vildagliptin reduced the stenosis of injured carotid arteries in diabetic mice, and this effect was achieved via inhibiting the activation of ER stress/NF-κB pathway.

Keywords: vildagliptin, VSMCs proliferation, phospho-IRE-1, phospho-p65, phospho-IKKα/β

Received: 13 Apr 2018; Accepted: 06 Feb 2019.

Edited by:

Pedro D'Orléans-Juste, Université de Sherbrooke, Canada

Reviewed by:

Francesco Rossi, Università degli Studi della Campania Luigi Vanvitelli Caserta, Italy
Stefania Tacconelli, Università degli Studi G. d'Annunzio Chieti e Pescara, Italy  

Copyright: © 2019 Ji, Ge, Xu, Ye, Fan, Zhang, Mei, Zhang, Ying, Yang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: MD, PhD. Chunjian Li, First Affiliated Hospital, Nanjing Medical University, Nanjing, China, lijay@njmu.edu.cn