Abstract

Background: Restenosis and atherosclerosis are chronic inflammatory disease. Abnormal vascular smooth muscle cell (VSMC) proliferation and migration play crucial roles in neointimal hyperplasia and restenosis progression in response to stimulation with various inflammatory cytokines, such as platelet-derived growth factor-BB (PDGF-BB) and tumour necrosis factor-α (TNF-α). Hydroxygenkwanin (HGK) exerts remarkable anti-inflammatory, antitumour, antiproliferative and antimigratory effects. The aim of the study was to evaluate and elucidate the therapeutic effect and regulatory mechanism of HGK on neointimal hyperplasia. Methods: To determine the therapeutic effects of HGK in PDGF-BB- or TNF-α-treated VSMCs, MTT assays, Western blotting analysis, cell cycle analysis, BrdU incorporation assay, wound healing assay and adhesion assay were performed in vitro. A docking assay was also used to elucidate the mechanism underlying the regulatory effect of HGK. Histological and immunohistochemical staining of denuded femoral arteries was conducted to elucidate the therapeutic effect of HGK in an in vivo assay. Results: HGK inhibited the abnormal proliferation, migration, and inflammation of PDGF-BB-or TNF-α-treated VSMCs through regulation of the PDK1/AKT/mTOR pathway. In addition, HGK promoted circulating endothelial progenitor cell (EPC) chemotaxis. In an in vivo assay, HGK dramatically enhanced re-endothelization and reduced neointimal hyperplasia after femoral artery denudation with a guide wire in mice. Conclusions: In the present study, HGK decreased the PDGF-BB- or TNF-α-induced abnormal proliferation, migration and inflammation in VSMCs and improved re-endothelialization and neointimal hyperplasia in denuded femoral arteries. These results provide a novel potential treatment for restenosis in the future.

Competing Interest Statement

The authors have declared no competing interest.

Details

Title
Effect of flavonoids hydroxygenkwanin on vascular smooth muscle cell proliferation, migration, and neointimal formation
Author
Chen, Chin-Chuan; Mao-Shin, Lin; Pin-Yu, Chen; Leu, Yann-Lii; Wang, Shu-Huei
University/institution
Cold Spring Harbor Laboratory Press
Section
New Results
Publication year
2022
Publication date
Dec 20, 2022
Publisher
Cold Spring Harbor Laboratory Press
ISSN
2692-8205
Source type
Working Paper
Language of publication
English
ProQuest document ID
2755967303
Copyright
© 2022. This article is published under http://creativecommons.org/licenses/by/4.0/ (“the License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.