TY - JOUR
T1 - The regulation of miRNAs by reconstituted high-density lipoproteins in diabetes-impaired angiogenesis
AU - Hourigan, Samuel T.
AU - Solly, Emma L.
AU - Nankivell, Victoria A.
AU - Ridiandries, Anisyah
AU - Weimann, Benjamin M.
AU - Henriquez, Rodney
AU - Tepper, Edward R.
AU - Zhang, Jennifer Q.J.
AU - Tsatralis, Tania
AU - Clayton, Zoe E.
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.
N1 - Funding Information:
Competing Interests: This work was supported by the National Health and Medical Research Council (NHMRC) of Australia Project Grant (#632512 to M.K.C.N. and C.A.B.); the National Heart Foundation Career Development Fellowship (#CR07S3331 to C.A.B.), and Ph.D. Scholarship (#PB12S6959 to L.Z.V.); and Diabetes Australia Research Trust (Y17G-TANJ to J.T.M.T). S.T.H., E.L.S., V.A.N., A.R., B.M.W., R.H., E.R.T., J.Q.J.Z., T.T., Z.E.C., S.R. and S.J.N declare no competing interests.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85053177272&partnerID=8YFLogxK
U2 - 10.1038/s41598-018-32016-x
DO - 10.1038/s41598-018-32016-x
M3 - Article
C2 - 30206364
AN - SCOPUS:85053177272
VL - 8
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 13596
ER -