Activation of Angiogenesis and Wound Healing in Diabetic Mice Using NO-Delivery Dinitrosyl Iron Complexes

Yu Jen Chen, Shou Cheng Wu, Hsiang Ching Wang, Tung Ho Wu, Shyng Shiou F. Yuan, Tsai Te Lu, Wen Feng Liaw, Yun Ming Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


In diabetes, abnormal angiogenesis due to hyperglycemia and endothelial dysfunction impairs wound healing and results in high risks of diabetic foot ulcers and mortality. Alternative therapeutic methods were attempted to prevent diabetic complications through the activation of endothelial nitric oxide synthase. In this study, direct application of nitric oxide using dinitrosyl iron complexes (DNICs) to promote angiogenesis and wound healing under physiological conditions and in diabetic mice is investigated. Based on in vitro and in vivo studies, DNIC [Fe2(μ-SCH2CH2OH)2(NO)4] (DNIC-1) with a sustainable NO-release reactivity (t1/2 = 27.4 ± 0.5 h at 25 °C and 16.8 ± 1.8 h at 37 °C) activates the NO-sGC-cGMP pathway and displays the best pro-angiogenesis activity overwhelming other NO donors and the vascular endothelial growth factor. Moreover, this pro-angiogenesis effect of DNIC-1 restores the impaired angiogenesis in the ischemic hind limb and accelerates the recovery rate of wound closure in diabetic mice. This study translates synthetic DNIC-1 into a novel therapeutic agent for the treatment of diabetes and highlights its sustainable δNO-release reactivity on the activation of angiogenesis and wound healing.

Original languageEnglish
Pages (from-to)4241-4251
Number of pages11
JournalMolecular Pharmaceutics
Issue number10
StatePublished - Aug 2019


  • angiogenesis
  • growth factors
  • nitric oxide
  • wound healing


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