Therapeutic manipulation of angiogenesis with miR-27b

Dorina Veliceasa, Dauren Biyashev, Gangjian Qin, Sol Misener, Alexander Roy Mackie, Raj Kishore, Olga V. Volpert*

*Corresponding author for this work

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number6
JournalVascular Cell
Volume7
Issue number1
DOIs
StatePublished - Jun 24 2015

Keywords

  • Cancer
  • Cardiovascular
  • Ischemia
  • Therapeutic angiogenesis
  • miR-27b
  • miRNA

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Computer Networks and Communications
  • Cell Biology

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  • Cite this

    Veliceasa, D., Biyashev, D., Qin, G., Misener, S., Mackie, A. R., Kishore, R., & Volpert, O. V. (2015). Therapeutic manipulation of angiogenesis with miR-27b. Vascular Cell, 7(1), [6]. https://doi.org/10.1186/s13221-015-0031-1