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Type: Journal article
Title: The regulation of miRNAs by reconstituted high-density lipoproteins in diabetes-impaired angiogenesis
Author: Hourigan, S.
Solly, E.
Nankivell, V.
Ridiandries, A.
Weimann, B.
Henriquez, R.
Tepper, E.
Zhang, J.
Tsatralis, T.
Clayton, Z.
Vanags, L.
Robertson, S.
Nicholls, S.
Ng, M.
Bursill, C.
Tan, J.
Citation: Scientific Reports, 2018; 8(1):13596
Publisher: Nature Publishing Group
Issue Date: 2018
ISSN: 2045-2322
Statement of
Samuel T. Hourigan, Emma L. Solly, Victoria A. Nankivell, Anisyah Ridiandries, Benjamin M. Weimann, Rodney Henriquez, Edward R. Tepper, Jennifer Q. J. Zhang, Tania Tsatralis, Zoe E. Clayton, Laura Z. Vanags, Stacy Robertson, Stephen J. Nicholls, Martin K. C. Ng, Christina A. Bursill, Joanne T. M. Tan
Abstract: 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.
Keywords: Cell Line; Animals; Humans; Mice; Diabetic Angiopathies; Diabetes Mellitus, Experimental; Lipoproteins, HDL; MicroRNAs; Neovascularization, Physiologic; Male
Rights: © The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
RMID: 0030098254
DOI: 10.1038/s41598-018-32016-x
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Appears in Collections:Medicine publications

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