title: Induction of thoracic aortic remodeling by endothelial-specific deletion of microRNA-21 in mice.
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.
authors.affiliation: Institute of Mechanobiology & Medical Engineering, School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xing-Yi
authors.initials: XY
authors.lastname: Zhang
authors.forename: Bao-Rong
authors.initials: BR
authors.lastname: Shen
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Zhang
authors.forename: Xue-Jiao
authors.initials: XJ
authors.lastname: Wan
authors.forename: Qing-Ping
authors.initials: QP
authors.lastname: Yao
authors.forename: Guang-Liang
authors.initials: GL
authors.lastname: Wu
authors.forename: Ji-Yao
authors.initials: JY
authors.lastname: Wang
authors.forename: Si-Guo
authors.initials: SG
authors.lastname: Chen
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Yan
authors.forename: Zong-Lai
authors.initials: ZL
authors.lastname: Jiang
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D001794:Blood Pressure / Q000235:genetics; D003094:Collagen / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D023061:Gene Order; D018390:Gene Targeting; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs; D051899:Smad2 Protein / Q000378:metabolism; D051902:Smad5 Protein / Q000378:metabolism; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C531950:MIRN21 microRNA, mouse; D035683:MicroRNAs; D051899:Smad2 Protein; D051902:Smad5 Protein; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D003094:Collagen; D004549:Elastin; D020782:Matrix Metalloproteinases; D000109:Acetylcholine