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MicroRNA-145, a novel smooth muscle cell phenotypic marker and modulator, controls vascular neointimal lesion formation.

Authors: Cheng, Yunhui  Liu, Xiaojun  Yang, Jian  Lin, Ying  Xu, Da-Zhong  Lu, Qi  Deitch, Edwin A  Huo, Yuqing  Delphin, Ellise S  Zhang, Chunxiang 
Citation: Cheng Y, etal., Circ Res. 2009 Jul 17;105(2):158-66. doi: 10.1161/CIRCRESAHA.109.197517. Epub 2009 Jun 18.
Pubmed: (View Article at PubMed) PMID:19542014
DOI: Full-text: DOI:10.1161/CIRCRESAHA.109.197517

Phenotypic modulation of vascular smooth muscle cells (VSMCs) plays a critical role in the pathogenesis of a variety of proliferative vascular diseases. Recently, we have found that microRNA (miRNA) miR-145 is the most abundant miRNA in normal vascular walls and in freshly isolated VSMCs; however, the role of miR-145 in VSMC phenotypic modulation and vascular diseases is currently unknown. Here we find that miR-145 is selectively expressed in VSMCs of the vascular wall and its expression is significantly downregulated in the vascular walls with neointimal lesion formation and in cultured dedifferentiated VSMCs. More importantly, both in cultured rat VSMCs in vitro and in balloon-injured rat carotid arteries in vivo, we demonstrate that the noncoding RNA miR-145 is a novel phenotypic marker and a novel phenotypic modulator of VSMCs. VSMC differentiation marker genes such as SM alpha-actin, calponin, and SM-MHC are upregulated by premiR-145 or adenovirus expressing miR-145 (Ad-miR-145) but are downregulated by the miR-145 inhibitor 2'OMe-miR-145. We have further identified that miR-145-mediated phenotypic modulation of VSMCs is through its target gene KLF5 and its downstream signaling molecule, myocardin. Finally, restoration of miR-145 in balloon-injured arteries via Ad-miR-145 inhibits neointimal growth. We conclude that miR-145 is a novel VSMC phenotypic marker and modulator that is able of controlling vascular neointimal lesion formation. These novel findings may have extensive implications for the diagnosis and therapy of a variety of proliferative vascular diseases.

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CRRD Object Information
CRRD ID: 13210556
Created: 2017-09-02
Species: All species
Last Modified: 2017-09-02
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.