MicroRNA-146a Regulates Perfusion Recovery in Response to Arterial Occlusion via Arteriogenesis
The growth of endogenous collateral arteries that bypass arterial occlusion(s), or arteriogenesis, is a fundamental shear stress-induced adaptation with implications for treating peripheral arterial disease. MicroRNAs (miRs) are key regulators of gene expression in response to injury and have strong...
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| Format: | Article |
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Frontiers Media S.A.
2018-01-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fbioe.2018.00001/full |
| _version_ | 1819078443629805568 |
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| author | Joshua L. Heuslein Joshua L. Heuslein Stephanie P. McDonnell Ji Song Brian H. Annex Brian H. Annex Richard J. Price Richard J. Price |
| author_facet | Joshua L. Heuslein Joshua L. Heuslein Stephanie P. McDonnell Ji Song Brian H. Annex Brian H. Annex Richard J. Price Richard J. Price |
| author_sort | Joshua L. Heuslein |
| collection | DOAJ |
| description | The growth of endogenous collateral arteries that bypass arterial occlusion(s), or arteriogenesis, is a fundamental shear stress-induced adaptation with implications for treating peripheral arterial disease. MicroRNAs (miRs) are key regulators of gene expression in response to injury and have strong therapeutic potential. In a previous study, we identified miR-146a as a candidate regulator of vascular remodeling. Here, we tested whether miR-146a regulates in vitro angiogenic endothelial cell (EC) behaviors, as well as perfusion recovery, arteriogenesis, and angiogenesis in response to femoral arterial ligation (FAL) in vivo. We found miR-146a inhibition impaired EC tube formation and migration in vitro. Following FAL, Balb/c mice were treated with a single, intramuscular injection of anti-miR-146a or scramble locked nucleic acid (LNA) oligonucleotides directly into the non-ischemic gracilis muscles. Serial laser Doppler imaging demonstrated that anti-miR-146a treated mice exhibited significantly greater perfusion recovery (a 16% increase) compared mice treated with scramble LNA. Moreover, anti-miR-146a treated mice exhibited a 22% increase in collateral artery diameter compared to controls, while there was no significant effect on in vivo angiogenesis or muscle regeneration. Despite exerting no beneficial effects on angiogenesis, the inhibition of mechanosensitive miR-146a enhances perfusion recovery after FAL via enhanced arteriogenesis. |
| first_indexed | 2024-12-21T19:13:11Z |
| format | Article |
| id | doaj.art-0d4a7ed7344747ed97097674b4031418 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-21T19:13:11Z |
| publishDate | 2018-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-0d4a7ed7344747ed97097674b40314182022-12-21T18:53:08ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852018-01-01610.3389/fbioe.2018.00001325999MicroRNA-146a Regulates Perfusion Recovery in Response to Arterial Occlusion via ArteriogenesisJoshua L. Heuslein0Joshua L. Heuslein1Stephanie P. McDonnell2Ji Song3Brian H. Annex4Brian H. Annex5Richard J. Price6Richard J. Price7Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, United StatesRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, United StatesRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, United StatesDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA, United StatesDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA, United StatesRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, United StatesDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA, United StatesRobert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA, United StatesThe growth of endogenous collateral arteries that bypass arterial occlusion(s), or arteriogenesis, is a fundamental shear stress-induced adaptation with implications for treating peripheral arterial disease. MicroRNAs (miRs) are key regulators of gene expression in response to injury and have strong therapeutic potential. In a previous study, we identified miR-146a as a candidate regulator of vascular remodeling. Here, we tested whether miR-146a regulates in vitro angiogenic endothelial cell (EC) behaviors, as well as perfusion recovery, arteriogenesis, and angiogenesis in response to femoral arterial ligation (FAL) in vivo. We found miR-146a inhibition impaired EC tube formation and migration in vitro. Following FAL, Balb/c mice were treated with a single, intramuscular injection of anti-miR-146a or scramble locked nucleic acid (LNA) oligonucleotides directly into the non-ischemic gracilis muscles. Serial laser Doppler imaging demonstrated that anti-miR-146a treated mice exhibited significantly greater perfusion recovery (a 16% increase) compared mice treated with scramble LNA. Moreover, anti-miR-146a treated mice exhibited a 22% increase in collateral artery diameter compared to controls, while there was no significant effect on in vivo angiogenesis or muscle regeneration. Despite exerting no beneficial effects on angiogenesis, the inhibition of mechanosensitive miR-146a enhances perfusion recovery after FAL via enhanced arteriogenesis.http://journal.frontiersin.org/article/10.3389/fbioe.2018.00001/fullmicroRNAperipheral arterial diseaseangiogenesisarteriogenesisendothelial cellshear stress |
| spellingShingle | Joshua L. Heuslein Joshua L. Heuslein Stephanie P. McDonnell Ji Song Brian H. Annex Brian H. Annex Richard J. Price Richard J. Price MicroRNA-146a Regulates Perfusion Recovery in Response to Arterial Occlusion via Arteriogenesis Frontiers in Bioengineering and Biotechnology microRNA peripheral arterial disease angiogenesis arteriogenesis endothelial cell shear stress |
| title | MicroRNA-146a Regulates Perfusion Recovery in Response to Arterial Occlusion via Arteriogenesis |
| title_full | MicroRNA-146a Regulates Perfusion Recovery in Response to Arterial Occlusion via Arteriogenesis |
| title_fullStr | MicroRNA-146a Regulates Perfusion Recovery in Response to Arterial Occlusion via Arteriogenesis |
| title_full_unstemmed | MicroRNA-146a Regulates Perfusion Recovery in Response to Arterial Occlusion via Arteriogenesis |
| title_short | MicroRNA-146a Regulates Perfusion Recovery in Response to Arterial Occlusion via Arteriogenesis |
| title_sort | microrna 146a regulates perfusion recovery in response to arterial occlusion via arteriogenesis |
| topic | microRNA peripheral arterial disease angiogenesis arteriogenesis endothelial cell shear stress |
| url | http://journal.frontiersin.org/article/10.3389/fbioe.2018.00001/full |
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