Cell-Specific Effects of GATA (GATA Zinc Finger Transcription Factor Family)-6 in Vascular Smooth Muscle and Endothelial Cells on Vascular Injury Neointimal Formation

Cell-Specific Effects of GATA (GATA Zinc Finger Transcription Factor Family)-6 in Vascular Smooth Muscle and Endothelial Cells on Vascular Injury Neointimal Formation.

Full text not available from this repository.
Item Type: Article
Status: Published
Official URL: https://doi.org/10.1161/ATVBAHA.118.312263
Journal or Publication Title: Arteriosclerosis, Thrombosis, and Vascular Biology
Volume: 39
Number: 5
Page Range: pp. 888-901
Date: 2019
Divisions: Cell Signalling
Depositing User: General Admin
Identification Number: 10.1161/ATVBAHA.118.312263
ISSN: 1079-5642
Date Deposited: 21 Dec 2020 22:42

Objective - Transcription factor GATA (GATA zinc finger transcription factor family)-6 is highly expressed in vessels and rapidly downregulated in balloon-injured carotid arteries and viral delivery of GATA-6 to the vessels limited the neointimal formation, however, little is known about its cell-specific regulation of in vivo vascular smooth muscle cell (VSMC) phenotypic state contributing to neointimal formation. This study aims to determine the role of vascular cell-specific GATA-6 in ligation- or injury-induced neointimal hyperplasia in vivo.

Approach and Results - Endothelial cell and VSMC-specific GATA-6 deletion mice are generated, and the results indicate that endothelial cell-specific GATA-6 deletion mice exhibit significant decrease of VSMC proliferation and attenuation of neointimal formation after artery ligation and injury compared with the wild-type littermate control mice. PDGF (platelet-derived growth factor)-B is identified as a direct target gene, and endothelial cell-GATA-6-PDGF-B pathway regulates VSMC proliferation and migration in a paracrine manner which controls the neointimal formation. In contrast, VSMC-specific GATA-6 deletion promotes injury-induced VSMC transformation from contractile to proliferative synthetic phenotype leading to increased neointimal formation. CCN (cysteine-rich 61/connective tissue growth factor/nephroblastoma overexpressed family)-5 is identified as a novel target gene, and VSMC-specific CCN-5 overexpression in mice reverses the VSMC-GATA-6 deletion-mediated increased cell proliferation and migration and finally attenuates the neointimal formation. Conclusions- This study gives us a direct in vivo evidence of GATA-6 cell lineage-specific regulation of PDGF-B and CCN-5 on VSMC phenotypic state, proliferation and migration contributing to neointimal formation, which advances our understanding of in vivo neointimal hyperplasia, meanwhile also provides opportunities for future therapeutic interventions.

Keywords: carotid arteries; cell lineage; endothelial cells; hyperplasia; transcription factors.

Zhuang, Tao
Liu, Jie
Chen, Xiaoli
Pi, Jingjiang
Kuang, Yashu
Wang, Yanfang
Tomlinson, Brain
Chan, Paul
Zhang, Qi
Li, Ying
Yu, Zuoren
Zheng, Xiangjian
Reilly, Muredach
Morrisey, Edward
Zhang, Lin
Liu, Zhongmin
Zhang, Yuzhen
Last Modified: 21 Dec 2020 22:42
URI: https://eprints.centenary.org.au/id/eprint/234

Actions (login required)

View Item View Item