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Keywords:

  • angiogenesis;
  • insulin-like growth factor 1;
  • microarray;
  • microRNA;
  • myocardial microvascular endothelial cells;
  • type 2 diabetes

SUMMARY

  • 1
    The aim of the present study was to determine the role of myocardial microvascular endothelial cells (MMVEC) in impaired angiogenesis of type 2 diabetic Goto-Kakizaki (GK) rats.
  • 2
    A microRNA (miRNA) microarray was used to assess miRNA expression in MMVEC from GK and Wistar rats. Upregulation of miRNA-320 was observed in MMVEC from GK rats using real-time reverse transcription–polymerase chain reaction (RT-PCR).
  • 3
    So far, nine miRNAs have been reported to target angiogenic factors and/or receptors, including kinase insert domain containing receptor (Flk-1), insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 1 receptor (IGF-1R). The predicted genes targeted by miR-320 include Flk-1, IGF-1 and IGF-1R. Western blot analysis and RT-PCR were used to analyse the protein and mRNA expression, respectively, of the putative genes IGF-1 and IGF-1R. The expression of IGF-1 and IGF-1R proteins decreased significantly in diabetic MMVEC. However, the expression of IGF-1 mRNA increased rather than decreased. The mRNA expression of IGF-1R did not differ significantly between diabetic and control MMVEC.
  • 4
    Transfection of an miR-320 inhibitor into MMVEC from GK rats confirmed that miR-320 impaired angiogenesis. The proliferation and migration of diabetic MMVEC improved after transfection of the miR-320 inhibitor. In addition, the miR-320 inhibitor significantly increased the expression of IGF-1 protein, but had no effect on the expression of IGF-1R.
  • 5
    Eleven miRNAs were upregulated in MMVEC from GK rats compared with those in Wistar rats: let-7e, miR-129, miR-291-5p, miR-320, miR-327, mir-333, miR-363–5p, miR-370, miR-494, miR-503 and miR-664.
  • 6
    The results indicate that upregulation of miR-320 in MMVEC from GK rats may be responsible for the inconsistency between the expression of IGF-1 protein and mRNA and therefore related to impaired angiogenesis in diabetes. Transfection of an miR-320 inhibitor may be a therapeutic approach for the treatment of impaired angiogenesis in diabetes.