MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation

Ruirui Ji, Yunhui Cheng, Junming Yue, Jian Yang, Xiaojun Liu, He Chen, David B. Dean, Chunxiang Zhang

Research output: Contribution to journalArticle

678 Citations (Scopus)

Abstract

MicroRNAs (miRNAs) are a recently discovered class of endogenous, small, noncoding RNAs that regulate about 30% of the encoding genes of the human genome. However, the role of miRNAs in vascular disease is currently completely unknown. Using microarray analysis, we demonstrated for the first time that miRNAs are aberrantly expressed in the vascular walls after balloon injury. The aberrantly expressed miRNAs were further confirmed by Northern blot and quantitative real-time polymerase chain reaction. Modulating an aberrantly overexpressed miRNA, miR-21, via antisense-mediated depletion (knock-down) had a significant negative effect on neointimal lesion formation. In vitro, the expression level of miR-21 in dedifferentiated vascular smooth muscle cells was significantly higher than that in fresh isolated differentiated cells. Depletion of miR-21 resulted in decreased cell proliferation and increased cell apoptosis in a dose-dependent manner. MiR-21-mediated cellular effects were further confirmed in vivo in balloon-injured rat carotid arteries. Western blot analysis demonstrated that PTEN and Bcl-2 were involved in miR-21-mediated cellular effects. The results suggest that miRNAs are novel regulatory RNAs for neointimal lesion formation. MiRNAs may be a new therapeutic target for proliferative vascular diseases such as atherosclerosis, postangioplasty restenosis, transplantation arteriopathy, and stroke.

Original languageEnglish (US)
Pages (from-to)1579-1588
Number of pages10
JournalCirculation research
Volume100
Issue number11
DOIs
StatePublished - Jun 1 2007
Externally publishedYes

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MicroRNAs
Blood Vessels
Vascular Diseases
Small Untranslated RNA
Human Genome
Microarray Analysis
Vascular Smooth Muscle
Carotid Arteries
Northern Blotting
Smooth Muscle Myocytes
Real-Time Polymerase Chain Reaction
Atherosclerosis
Transplantation
Western Blotting
Stroke
Cell Proliferation
RNA
Apoptosis
Wounds and Injuries
Genes

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation. / Ji, Ruirui; Cheng, Yunhui; Yue, Junming; Yang, Jian; Liu, Xiaojun; Chen, He; Dean, David B.; Zhang, Chunxiang.

In: Circulation research, Vol. 100, No. 11, 01.06.2007, p. 1579-1588.

Research output: Contribution to journalArticle

Ji, Ruirui ; Cheng, Yunhui ; Yue, Junming ; Yang, Jian ; Liu, Xiaojun ; Chen, He ; Dean, David B. ; Zhang, Chunxiang. / MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation. In: Circulation research. 2007 ; Vol. 100, No. 11. pp. 1579-1588.
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