Induction of Thoracic Aortic Remodeling by Endothelial-specific Deletion of MicroRNA-21 in Mice

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2013 Mar 26

PMID 23527070

Citations 13

Authors

Xing-Yi Zhang

Bao-Rong Shen

Yu-Cheng Zhang

Xue-Jiao Wan

Qing-Ping Yao

Guang-Liang Wu

Ji-Yao Wang

Si-Guo Chen

Zhi-Qiang Yan

Zong-Lai Jiang

Affiliations

Soon will be listed here.

Abstract

MicroRNAs (miRs) are known to have an important role in modulating vascular biology. MiR21 was found to be involved in the pathogenesis of proliferative vascular disease. The role of miR21 in endothelial cells (ECs) has well studied in vitro, but the study in vivo remains to be elucidated. In this study, miR21 endothelial-specific knockout mice were generated by Cre/LoxP system. Compared with wild-type mice, the miR21 deletion in ECs resulted in structural and functional remodeling of aorta significantly, such as diastolic pressure dropping, maximal tension depression, endothelium-dependent relaxation impairment, an increase of opening angles and wall-thickness/inner diameter ratio, and compliance decrease, in the miR21 endothelial-specific knockout mice. Furthermore, the miR21 deletion in ECs induced down-regulation of collagen I, collagen III and elastin mRNA and proteins, as well as up-regulation of Smad7 and down-regulation of Smad2/5 in the aorta of miR21 endothelial-specific knockout mice. CTGF and downstream MMP/TIMP changes were also identified to mediate vascular remodeling. The results showed that miR21 is identified as a critical molecule to modulate vascular remodeling, which will help to understand the role of miR21 in vascular biology and the pathogenesis of vascular diseases.

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