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

• Published in: Scientific reports Vol. 8; no. 1; pp. 13596 - 14
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.09.2018; Nature Publishing Group
• Subjects: 13; 13/106; 13/109; 13/51; 38/39; 38/77; 64/60; 692/163/2743/137/138; 692/4019/592/16; 82/29; Angiogenesis; Diabetes; Diabetes mellitus; High density lipoprotein; Humanities and Social Sciences; Ischemia; Lipoproteins; miRNA; multidisciplinary; Plasma levels; Rodents; Science; Science (multidisciplinary); antimiR; Ischaemic Site; Diabetes-related Vascular Complications; Anti-angiogenic Role; Angiogenic miRNAs
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-018-32016-x

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.