title: In situ eNOS/NO up-regulation-a simple and effective therapeutic strategy for diabetic skin ulcer.
abstract: Decreased nitric oxide (NO) synthesis and increased NO consumption in diabetes induces the inadequate blood flow to tissues that is primarily responsible for the pathogenesis and refractoriness of diabetic skin ulcers. The present study proposed a simple and effective therapeutic strategy for diabetic skin ulcers-in situ up-regulation of endothelial nitric oxide synthase (eNOS) expression and NO synthesis by statin-loaded tissue engineering scaffold (TES). In vitro experiments on human umbilical vein endothelial cells indicated that the statin-loaded TES relieved the high-glucose induced decrease in cell viability and promoted NO synthesis under high-glucose conditions. In a rat model of diabetes, the statin-loaded TES promoted eNOS expression and NO synthesis in/around the regenerated tissues. Subsequently, accelerated vascularization and elevated blood supply were observed, followed by rapid wound healing. These findings suggest that the in situ up-regulation of eNOS/NO by a statin-loaded TES may be a useful therapeutic method for intractable diabetic skin wounds.
authors.affiliation: School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.|Key Laboratory of Xin'an Medicine, Ministry of Education, Hefei 230031, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.|Key Laboratory of Xin'an Medicine, Ministry of Education, Hefei 230031, China.
authors.forename: Dengke
authors.initials: D
authors.lastname: Yin
authors.affiliation: School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.
authors.forename: Ziyan
authors.initials: Z
authors.lastname: Hou
authors.affiliation: Key Laboratory of Xin'an Medicine, Ministry of Education, Hefei 230031, China.|Department of Endocrinology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei 230031, China.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Fang
mesh_terms: D000818:Animals; D001786:Blood Glucose; D002470:Cell Survival / Q000187:drug effects; D048909:Diabetes Complications; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D004195:Disease Models, Animal; D004337:Drug Carriers; D065546:Drug Liberation; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D008148:Lovastatin / Q000008:administration & dosage; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D012883:Skin Ulcer / Q000209:etiology* / Q000378:metabolism* / Q000628:therapy; D054457:Tissue Scaffolds / Q000737:chemistry; D014945:Wound Healing
chemical_list: D001786:Blood Glucose; D004337:Drug Carriers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D008148:Lovastatin; D052250:Nitric Oxide Synthase Type III; D005947:Glucose