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Cardiovascular Drugs and Therapy
Published in: Cardiovascular Drugs and Therapy 1/2019

01-02-2019 | ORIGINAL ARTICLE

The Role of Tauroursodeoxycholic Acid on Dedifferentiation of Vascular Smooth Muscle Cells by Modulation of Endoplasmic Reticulum Stress and as an Oral Drug Inhibiting In-Stent Restenosis

Authors: Hangqi Luo, Changzuan Zhou, Jufang Chi, Sunlei Pan, Hui Lin, Feidan Gao, Tingjuan Ni, Liping Meng, Jie Zhang, Chengjian Jiang, Zheng Ji, Haitao Lv, Hangyuan Guo

Published in: Cardiovascular Drugs and Therapy | Issue 1/2019

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Abstract

Purpose

The role of endoplasmic reticulum (ER) stress in cardiovascular disease is now recognized. Tauroursodeoxycholic acid (TUDCA) is known to have cardiovascular protective effects by decreasing ER stress. This study aimed to assess the ability of TUDCA to decrease ER stress, inhibit dedifferentiation of vascular smooth muscle cells (VSMCs), and reduce in-stent restenosis.

Methods

The effect of TUDCA on dedifferentiation of VSMCs and ER stress was investigated in vitro using wound-healing assays, MTT assays, and western blotting. For in vivo studies, 18 rabbits were fed an atherogenic diet to induce atheroma formation. Bare metal stents (BMS), BMS+TUDCA or Firebird stents were implanted in the left common carotid artery. Rabbits were euthanized after 28 days and processed for scanning electron microscope (SEM), histological examination (HE), and immunohistochemistry.

Results

In vitro TUDCA (10–1000 μmol/L) treatment significantly inhibited platelet-derived growth factor (PDGF)-BB-induced proliferation and migration in VSMCs in a concentration-dependent manner and decreased ER stress markers (IRE1, XBP1, KLF4, and GRP78). In vivo, we confirmed no significant difference in neointimal coverage on three stents surfaces; neointimal was significantly lower with BMS+TUDCA (1.6 ± 0.2 mm2) compared with Firebird (1.90 ± 0.1 mm2) and BMS (2.3 ± 0.1 mm2). Percent stenosis was lowest for BMS+TUDCA, then Firebird, and was significantly higher with BMS (28 ± 4%, 35 ± 7%, 40 ± 1%; respectively; P < 0.001). TUDCA treatment decreased ER stress in the BMS+TUDCA group compared with BMS.

Conclusions

TUDCA inhibited dedifferentiation of VSMCs by decreasing ER stress and reduced in-stent restenosis, possibly through downregulation of the IRE1/XBP1 signaling pathway.
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Metadata
Title
The Role of Tauroursodeoxycholic Acid on Dedifferentiation of Vascular Smooth Muscle Cells by Modulation of Endoplasmic Reticulum Stress and as an Oral Drug Inhibiting In-Stent Restenosis
Authors
Hangqi Luo
Changzuan Zhou
Jufang Chi
Sunlei Pan
Hui Lin
Feidan Gao
Tingjuan Ni
Liping Meng
Jie Zhang
Chengjian Jiang
Zheng Ji
Haitao Lv
Hangyuan Guo
Publication date
01-02-2019
Publisher
Springer US
Published in
Cardiovascular Drugs and Therapy / Issue 1/2019
Print ISSN: 0920-3206
Electronic ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-018-6844-4

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