標題: | Activation of Angiogenesis and Wound Healing in Diabetic Mice Using NO-Delivery Dinitrosyl Iron Complexes |
作者: | Chen, Yu-Jen Wu, Shou-Cheng Wang, Hsiang-Ching Wu, Tung-Ho Yuan, Shyng-Shiou F. Lu, Tsai-Te Liaw, Wen-Feng Wang, Yun-Ming 交大名義發表 National Chiao Tung University |
關鍵字: | nitric oxide;angiogenesis;wound healing;growth factors |
公開日期: | 1-十月-2019 |
摘要: | 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 [Fe-2(mu-SCH2CH2OH)(2)(NO)(4)] (DNIC-1) with a sustainable NO-release reactivity (t(1/2) = 27.4 +/- 0.5 h at 25 degrees C and 16.8 +/- 1.8 h at 37 degrees C) activates the NO-sGC-cGMP pathway and displays the best proangiogenesis 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 (NO)-N-center dot-release reactivity on the activation of angiogenesis and wound healing. |
URI: | http://dx.doi.org/10.1021/acs.molpharmaceut.9b00586 http://hdl.handle.net/11536/153136 |
ISSN: | 1543-8384 |
DOI: | 10.1021/acs.molpharmaceut.9b00586 |
期刊: | MOLECULAR PHARMACEUTICS |
Volume: | 16 |
Issue: | 10 |
起始頁: | 4241 |
結束頁: | 4251 |
顯示於類別: | 期刊論文 |