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Therapeutic manipulation of angiogenesis with miR-27b
BACKGROUND: Multiple studies demonstrated pro-angiogenic effects of microRNA (miR)-27b. Its targets include Notch ligand Dll4, Sprouty (Spry)-2, PPARγ and Semaphorin (SEMA) 6A. miR-27 effects in the heart are context-dependent: although it is necessary for ventricular maturation, targeted overexpres...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497374/ https://www.ncbi.nlm.nih.gov/pubmed/26161255 http://dx.doi.org/10.1186/s13221-015-0031-1 |
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author | Veliceasa, Dorina Biyashev, Dauren Qin, Gangjian Misener, Sol Mackie, Alexander Roy Kishore, Raj Volpert, Olga V. |
author_facet | Veliceasa, Dorina Biyashev, Dauren Qin, Gangjian Misener, Sol Mackie, Alexander Roy Kishore, Raj Volpert, Olga V. |
author_sort | Veliceasa, Dorina |
collection | PubMed |
description | BACKGROUND: Multiple studies demonstrated pro-angiogenic effects of microRNA (miR)-27b. Its targets include Notch ligand Dll4, Sprouty (Spry)-2, PPARγ and Semaphorin (SEMA) 6A. miR-27 effects in the heart are context-dependent: although it is necessary for ventricular maturation, targeted overexpression in cardiomyocytes causes hypertrophy and dysfunction during development. Despite significant recent advances, therapeutic potential of miR-27b in cardiovascular disease and its effects in adult heart remain unexplored. Here, we assessed the therapeutic potential of miR-27b mimics and inhibitors in rodent models of ischemic disease and cancer. METHODS: We have used a number of models to demonstrate the effects of miR-27b mimicry and inhibition in vivo, including subcutaneous Matrigel plug assay, mouse models of hind limb ischemia and myocardial infarction and subcutaneous Lewis Lung carcinoma. RESULTS: Using mouse model of myocardial infarction due to the coronary artery ligation, we showed that miR-27b mimic had overall beneficial effects, including increased vascularization, decreased fibrosis and increased ejection fraction. In mouse model of critical limb ischemia, miR-27b mimic also improved tissue re-vascularization and perfusion. In both models, miR-27b mimic clearly decreased macrophage recruitment to the site of hypoxic injury. In contrast, miR-27b increased the recruitment of bone marrow derived cells to the neovasculature, as was shown using mice reconstituted with fluorescence-tagged bone marrow. These effects were due, at least in part, to the decreased expression of Dll4, PPARγ and IL10. In contrast, blocking miR-27b significantly decreased vascularization and reduced growth of subcutaneous tumors and decreased BMDCs recruitment to the tumor vasculature. CONCLUSIONS: Our study demonstrates the utility of manipulating miR-27b levels in the treatment of cardiovascular disease and cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13221-015-0031-1) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4497374 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-44973742015-07-10 Therapeutic manipulation of angiogenesis with miR-27b Veliceasa, Dorina Biyashev, Dauren Qin, Gangjian Misener, Sol Mackie, Alexander Roy Kishore, Raj Volpert, Olga V. Vasc Cell Research BACKGROUND: Multiple studies demonstrated pro-angiogenic effects of microRNA (miR)-27b. Its targets include Notch ligand Dll4, Sprouty (Spry)-2, PPARγ and Semaphorin (SEMA) 6A. miR-27 effects in the heart are context-dependent: although it is necessary for ventricular maturation, targeted overexpression in cardiomyocytes causes hypertrophy and dysfunction during development. Despite significant recent advances, therapeutic potential of miR-27b in cardiovascular disease and its effects in adult heart remain unexplored. Here, we assessed the therapeutic potential of miR-27b mimics and inhibitors in rodent models of ischemic disease and cancer. METHODS: We have used a number of models to demonstrate the effects of miR-27b mimicry and inhibition in vivo, including subcutaneous Matrigel plug assay, mouse models of hind limb ischemia and myocardial infarction and subcutaneous Lewis Lung carcinoma. RESULTS: Using mouse model of myocardial infarction due to the coronary artery ligation, we showed that miR-27b mimic had overall beneficial effects, including increased vascularization, decreased fibrosis and increased ejection fraction. In mouse model of critical limb ischemia, miR-27b mimic also improved tissue re-vascularization and perfusion. In both models, miR-27b mimic clearly decreased macrophage recruitment to the site of hypoxic injury. In contrast, miR-27b increased the recruitment of bone marrow derived cells to the neovasculature, as was shown using mice reconstituted with fluorescence-tagged bone marrow. These effects were due, at least in part, to the decreased expression of Dll4, PPARγ and IL10. In contrast, blocking miR-27b significantly decreased vascularization and reduced growth of subcutaneous tumors and decreased BMDCs recruitment to the tumor vasculature. CONCLUSIONS: Our study demonstrates the utility of manipulating miR-27b levels in the treatment of cardiovascular disease and cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13221-015-0031-1) contains supplementary material, which is available to authorized users. BioMed Central 2015-06-24 /pmc/articles/PMC4497374/ /pubmed/26161255 http://dx.doi.org/10.1186/s13221-015-0031-1 Text en © Veliceasa et al. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Veliceasa, Dorina Biyashev, Dauren Qin, Gangjian Misener, Sol Mackie, Alexander Roy Kishore, Raj Volpert, Olga V. Therapeutic manipulation of angiogenesis with miR-27b |
title | Therapeutic manipulation of angiogenesis with miR-27b |
title_full | Therapeutic manipulation of angiogenesis with miR-27b |
title_fullStr | Therapeutic manipulation of angiogenesis with miR-27b |
title_full_unstemmed | Therapeutic manipulation of angiogenesis with miR-27b |
title_short | Therapeutic manipulation of angiogenesis with miR-27b |
title_sort | therapeutic manipulation of angiogenesis with mir-27b |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497374/ https://www.ncbi.nlm.nih.gov/pubmed/26161255 http://dx.doi.org/10.1186/s13221-015-0031-1 |
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