Journal article
MicroRNA-93 Controls Perfusion Recovery After Hindlimb Ischemia by Modulating Expression of Multiple Genes in the Cell Cycle Pathway
Circulation (New York, N.Y.), Vol.127(17), pp.1818-1828
04/30/2013
DOI: 10.1161/CIRCULATIONAHA.112.000860
PMCID: PMC3856290
PMID: 23559675
Abstract
Background-MicroRNAs are key regulators of gene expression in response to injury, but there is limited knowledge of their role in ischemia-induced angiogenesis, such as in peripheral arterial disease. Here, we used an unbiased strategy and took advantage of different phenotypic outcomes that follow surgically induced hindlimb ischemia between inbred mouse strains to identify key microRNAs involved in perfusion recovery from hindlimb ischemia.
Methods and Results-From comparative microRNA profiling between inbred mouse strains that display profound differences in their extent of perfusion recovery after hindlimb ischemia, we found that the mouse strain with higher levels of microRNA-93 (miR-93) in hindlimb muscle before ischemia and the greater ability to upregulate miR-93 in response to ischemia had better perfusion recovery. In vitro, overexpression of miR-93 attenuated hypoxia-induced apoptosis in both endothelial and skeletal muscle cells and enhanced proliferation in both cell types. In addition, miR-93 overexpression enhanced endothelial cell tube formation. In vivo, miR-93 overexpression enhanced capillary density and perfusion recovery from hindlimb ischemia, and antagomirs to miR-93 attenuated perfusion recovery. Both in vitro and in vivo modulation of miR-93 resulted in alterations in the expression of >1 cell cycle pathway gene in 2 different cell types.
Conclusions-Our data indicate that miR-93 enhances perfusion recovery from hindlimb ischemia by modulation of multiple genes that coordinate the functional pathways of cell proliferation and apoptosis. Thus, miR-93 is a strong potential target for pharmacological modulation to promote angiogenesis in ischemic tissue. (Circulation. 2013;127:1818-1828.)
Details
- Title: Subtitle
- MicroRNA-93 Controls Perfusion Recovery After Hindlimb Ischemia by Modulating Expression of Multiple Genes in the Cell Cycle Pathway
- Creators
- Surovi Hazarika - University of VirginiaCharles R. Farber - University of VirginiaAyotunde O. Dokun - University of VirginiaAchillieas N. Pitsillides - University of VirginiaTao Wang - University of VirginiaR. John Lye - University of VirginiaBrian H. Annex - University of Virginia
- Resource Type
- Journal article
- Publication Details
- Circulation (New York, N.Y.), Vol.127(17), pp.1818-1828
- DOI
- 10.1161/CIRCULATIONAHA.112.000860
- PMID
- 23559675
- PMCID
- PMC3856290
- NLM abbreviation
- Circulation
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 38
- Grant note
- 65847 / Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program; Robert Wood Johnson Foundation (RWJF) NHLBI R01 HL 101200; 3 RO1 HL101200-01S1 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01HL101200 / NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI)
- Language
- English
- Date published
- 04/30/2013
- Academic Unit
- Molecular Physiology and Biophysics; Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984297498702771
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