Induction of thoracic aortic remodeling by endothelial-specific deletion of microRNA-21 in mice

• Published in: PloS one 2013-03, Vol.8 (3), p.e59002
• Main Authors: Zhang, Xing-Yi, Shen, Bao-Rong, Zhang, Yu-Cheng, Wan, Xue-Jiao, Yao, Qing-Ping, Wu, Guang-Liang, Wang, Ji-Yao, Chen, Si-Guo, Yan, Zhi-Qiang, Jiang, Zong-Lai
• Format: Article
• Language: English
• Subjects: Acetylcholine - pharmacology; Animals; Aorta; Aorta, Thoracic - drug effects; Aorta, Thoracic - metabolism; Aorta, Thoracic - pathology; Apoptosis; Biology; Biotechnology; Blood pressure; Blood Pressure - genetics; Cell growth; Clonal deletion; Cloning; Collagen; Collagen (type I); Collagen (type III); Collagen - metabolism; Connective tissue growth factor; Connective Tissue Growth Factor - metabolism; Coronary vessels; Diastolic pressure; Elastin; Elastin - metabolism; Endothelial cells; Endothelium; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Engineering; Extracellular Matrix - metabolism; Female; Gene Deletion; Gene expression; Gene Order; Gene Targeting; Growth factors; Hypertension; In vivo methods and tests; Laboratory animals; Life sciences; Male; Matrix Metalloproteinases - metabolism; Medicine; Mental depression; Mice; Mice, Knockout; MicroRNA; MicroRNAs; miRNA; mRNA; Pathogenesis; Proteins; Ribonucleic acid; RNA; Rodents; Smad2 protein; Smad2 Protein - metabolism; Smad5 Protein - metabolism; Smad7 protein; Smooth muscle; Structure-function relationships; Thorax; Thrombosis; Time Factors; Tissue inhibitor of metalloproteinases; Transforming Growth Factor beta1 - metabolism; Transgenic animals; Vascular diseases
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0059002

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.