NOS1AP and Capon Associated Impaired Healing in Those with Diabetic Foot Ulcers

NOS1AP 和 Capon 与糖尿病足溃疡患者的愈合受损相关

• 批准号: 9925084
• 负责人: David Margolis
• 金额: $ 60.51万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9925084
• 关键词: Age; Amputation; Anatomy; Animals; Biochemical; Biological Process; Blood; Bone Marrow; Cell physiology; Cells; Characteristics; Chronic; Clinical; Code; Complications of Diabetes Mellitus; Data; Diabetes Mellitus; Diabetic Foot Ulcer; Disease; Endothelial Growth Factors Receptor; Endothelium; Engineering; Enrollment; Epidemic; Ethnic Origin; Family; Foot Ulcer; Gender; Genes; Genetic Variation; Geographic Locations; Goals; Hypoxia Inducible Factor; Impaired healing; Impaired wound healing; Impairment; Incidence; Individual; Infection; Inflammasome; Inflammatory; Interleukin-1 beta; Interleukin-18; Knowledge; Leukocytes; Link; Lower Extremity; Medicare; Neuropathy; Neutrophil Activation; Nitric Oxide Synthase; Pathway interactions; Patients; Peripheral Vascular Diseases; Phosphorylation; Platelet Activation; Population; Populations at Risk; Process; Production; Protein Kinase C; Protein Tyrosine Kinase; Proteins; Race; Receptor Activation; Recording of previous events; Research; Risk; Risk Factors; Single Nucleotide Polymorphism; Surveys; TXN gene; Time; Trauma; Variant; Vascular Endothelial Growth Factors; beneficiary; biobank; care costs; chronic wound; diabetic; foot; gain of function; genetic variant; healing; health management; high risk; immunoregulation; marenostrin; mortality risk; precursor cell; receptor; statistics; stem; stem cells; tissue repair; wound; wound care; wound healing

Project Summary/Abstract Diabetes mellitus has reached epidemic proportions. A significant complication of diabetes is impaired healing which results in diabetic foot ulcer (DFU) and lower extremity amputation (LEA). About 20% of those with diabetes will develop a DFU. The annual incidence of LEA in Medicare beneficiaries with diabetes is about 4 per thousand, but rates of LEA can vary up to two- to threefold by race/ethnicity, geographic location, and gender. Individuals with diabetes develop DFU and LEA for many reasons that probably include interactions or alterations in intrinsic pathways responsible for wound repair, the presence of infection, changes to immune regulation, neuropathy, peripheral vascular disease, changes in anatomic function of the foot, and local trauma. DFUs are chronic wounds, which are by definition are wounds that have failed to follow an orderly and timely sequence resulting in healing and have impaired healing. Those that develop chronic wounds that result in LEA have wounds that heal slowly or not at all. Why a wound becomes chronic is not well understood. In the past 5 years, we have developed preliminary evidence showing that genetic variation in NOS1AP, which codes for a protein called capon, is associated with impaired healing of DFU, an increased risk of LEA, and decrease in the number or circulating endothelial precursors cells, which have been shown to be associated with individuals with a DFU that are less likely to heal. Our project focuses on producing further evidence to confirm the association of NOS1AP variation with impaired healing and to discern the functional basis of NOS1AP genetic variation on capon and ultimately capon’s influence on wound repair. To that end, the goal of our present study is to explore the possibility that common genetic variants of NOS1AP in those who have diabetes are associated with alterations in wound repair.

项目总结/摘要 糖尿病已达到流行病的程度。糖尿病的一个重要并发症是 导致糖尿病足溃疡（DFU）和下肢截肢（莱亚）的愈合。其中大约20% 糖尿病患者会出现DFU。在患有糖尿病的医疗保险受益人中，莱亚的年发病率约为 4/1000，但莱亚的比率可能因种族/民族、地理位置和 性别.糖尿病患者发生DFU和莱亚的原因有很多，可能包括相互作用或 负责伤口修复的内在途径的改变，感染的存在，免疫系统的变化， 调节、神经病变、外周血管疾病、足部解剖功能的变化以及局部 外伤DFU是慢性伤口，根据定义，其是未能遵循有序和 及时的序列导致愈合和受损的愈合。那些形成慢性伤口的人， 在莱亚中，伤口愈合缓慢或根本不愈合。为什么伤口会变成慢性的，我们还不太清楚。 在过去的5年里，我们已经开发了初步的证据表明，NOS 1AP的遗传变异， 编码一种叫做阉鸡的蛋白质，与DFU的愈合受损，莱亚的风险增加， 以及循环内皮前体细胞数量的减少，这已经被证明是 与不太可能治愈的DFU患者相关。我们的项目重点是进一步生产 证实NOS 1AP变异与愈合受损的关联以及辨别功能性 鸡NOS 1AP基因变异的基础以及鸡对创伤修复的影响。为此目的， 我们目前研究的目的是探索在这些人中NOS 1AP的常见遗传变异的可能性， 与伤口修复的改变有关。