title: Antimycotic ciclopirox olamine in the diabetic environment promotes angiogenesis and enhances wound healing.
abstract: Diabetic wounds remain a major medical challenge with often disappointing outcomes despite the best available care. An impaired response to tissue hypoxia and insufficient angiogenesis are major factors responsible for poor healing in diabetic wounds. Here we show that the antimycotic drug ciclopirox olamine (CPX) can induce therapeutic angiogenesis in diabetic wounds. Treatment with CPX in vitro led to upregulation of multiple angiogenic genes and increased availability of HIF-1α. Using an excisional wound splinting model in diabetic mice, we showed that serial topical treatment with CPX enhanced wound healing compared to vehicle control treatment, with significantly accelerated wound closure, increased angiogenesis, and increased dermal cellularity. These findings offer a promising new topical pharmacologic therapy for the treatment of diabetic wounds.
authors: Hagey Laboratory for Regenerative Medicine, Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, California, United States of America.
authors: Sae Hee
authors: SH
authors: Ko
authors: Allison
authors: A
authors: Nauta
authors: Shane D
authors: SD
authors: Morrison
authors: Hongyan
authors: H
authors: Zhou
authors: Andrew
authors: A
authors: Zimmermann
authors: Geoffrey C
authors: GC
authors: Gurtner
authors: Sheng
authors: S
authors: Ding
authors: Michael T
authors: MT
authors: Longaker
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D000077768:Ciclopirox; D003920:Diabetes Mellitus / Q000503:physiopathology*; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D011728:Pyridones / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D000935:Antifungal Agents; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011728:Pyridones; D042461:Vascular Endothelial Growth Factor A; D000077768:Ciclopirox