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

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

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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.

LanguageEnglish
Article number13596
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - 1 Dec 2018

ASJC Scopus subject areas

  • General

Cite this

Hourigan, S. T., Solly, E. L., Nankivell, V. A., Ridiandries, A., Weimann, B. M., Henriquez, R., ... Tan, J. T. M. (2018). The regulation of miRNAs by reconstituted high-density lipoproteins in diabetes-impaired angiogenesis. Scientific Reports, 8(1), [13596]. https://doi.org/10.1038/s41598-018-32016-x
Hourigan, Samuel T. ; Solly, Emma L. ; Nankivell, Victoria A. ; Ridiandries, Anisyah ; Weimann, Benjamin M. ; Henriquez, Rodney ; Tepper, Edward R. ; Zhang, Jennifer Q.J. ; Tsatralis, Tania ; Clayton, Zoe E. ; Vanags, Laura Z. ; Robertson, Stacy ; Nicholls, Stephen J. ; Ng, Martin K.C. ; Bursill, Christina A. ; Tan, Joanne T.M. / The regulation of miRNAs by reconstituted high-density lipoproteins in diabetes-impaired angiogenesis. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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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.",
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Hourigan, ST, Solly, EL, Nankivell, VA, Ridiandries, A, Weimann, BM, Henriquez, R, Tepper, ER, Zhang, JQJ, Tsatralis, T, Clayton, ZE, Vanags, LZ, Robertson, S, Nicholls, SJ, Ng, MKC, Bursill, CA & Tan, JTM 2018, 'The regulation of miRNAs by reconstituted high-density lipoproteins in diabetes-impaired angiogenesis', Scientific Reports, vol. 8, no. 1, 13596. https://doi.org/10.1038/s41598-018-32016-x

The regulation of miRNAs by reconstituted high-density lipoproteins in diabetes-impaired angiogenesis. / Hourigan, Samuel T.; Solly, Emma L.; Nankivell, Victoria A.; Ridiandries, Anisyah; Weimann, Benjamin M.; Henriquez, Rodney; Tepper, Edward R.; Zhang, Jennifer Q.J.; Tsatralis, Tania; Clayton, Zoe E.; Vanags, Laura Z.; Robertson, Stacy; Nicholls, Stephen J.; Ng, Martin K.C.; Bursill, Christina A.; Tan, Joanne T.M.

In: Scientific Reports, Vol. 8, No. 1, 13596, 01.12.2018.

Research output: Contribution to journalArticle

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AU - Weimann, Benjamin M.

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AU - Tepper, Edward R.

AU - Zhang, Jennifer Q.J.

AU - Tsatralis, Tania

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AU - Vanags, Laura Z.

AU - Robertson, Stacy

AU - Nicholls, Stephen J.

AU - Ng, Martin K.C.

AU - Bursill, Christina A.

AU - Tan, Joanne T.M.

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AB - 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.

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Hourigan ST, Solly EL, Nankivell VA, Ridiandries A, Weimann BM, Henriquez R et al. The regulation of miRNAs by reconstituted high-density lipoproteins in diabetes-impaired angiogenesis. Scientific Reports. 2018 Dec 1;8(1). 13596. https://doi.org/10.1038/s41598-018-32016-x