The regulation of miRNAs by reconstituted high-density lipoproteins in diabetes-impaired angiogenesis

Hourigan, S. T. et al. (2018) The regulation of miRNAs by reconstituted high-density lipoproteins in diabetes-impaired angiogenesis. Scientific Reports, 8, 13596. (doi: 10.1038/s41598-018-32016-x) (PMID:30206364) (PMCID:PMC6133943)

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Diabetic vascular complications are associated with impaired ischaemia-driven angiogenesis. We recently found that reconstituted high-density lipoproteins (rHDL) rescue diabetes-impaired angiogenesis. microRNAs (miRNAs) regulate angiogenesis and are transported within HDL to sites of injury/repair. The role of miRNAs in the rescue of diabetes-impaired angiogenesis by rHDL is unknown. Using a miRNA array, we found that rHDL inhibits hsa-miR-181c-5p expression in vitro and using a hsa-miR-181c-5p mimic and antimiR identify a novel anti-angiogenic role for miR-181c-5p. miRNA expression was tracked over time post-hindlimb ischaemic induction in diabetic mice. Early post-ischaemia when angiogenesis is important, rHDL suppressed hindlimb mmu-miR-181c-5p. mmu-miR-181c-5p was not detected in the plasma or within HDL, suggesting rHDL specifically targets mmu-miR-181c-5p at the ischaemic site. Three known angiogenic miRNAs (mmu-miR-223-3p, mmu-miR-27b-3p, mmu-miR-92a-3p) were elevated in the HDL fraction of diabetic rHDL-infused mice early post-ischaemia. This was accompanied by a decrease in plasma levels. Only mmu-miR-223-3p levels were elevated in the hindlimb 3 days post-ischaemia, indicating that rHDL regulates mmu-miR-223-3p in a time-dependent and site-specific manner. The early regulation of miRNAs, particularly miR-181c-5p, may underpin the rescue of diabetes-impaired angiogenesis by rHDL and has implications for the treatment of diabetes-related vascular complications.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Robertson, Dr Stacy
Authors: Hourigan, S. T., Solly, E. L., Nankivell, V. A., Ridiandries, A., Weimann, B. M., Henriquez, R., Tepper, E. R., Zhang, J. Q.J., Tsatralis, T., Clayton, Z. E., Vanags, L. Z., Robertson, S., Nicholls, S. J., Ng, M. K.C., Bursill, C. A., and Tan, J. T.M.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Scientific Reports
Publisher:Nature Publishing Group
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Scientific Reports 8: 13596
Publisher Policy:Reproduced under a Creative Commons License

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