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

基本信息

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
项目类别：
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

项目摘要

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.

项目概要/摘要糖尿病已达到流行的程度，糖尿病的一个重要并发症是受损。其中约 20% 会导致糖尿病足溃疡 (DFU) 和下肢截肢 (LEA)。患有糖尿病的人将发展为 DFU 患有糖尿病的 Medicare 受益人中 LEA 的年发病率约为千分之 4，但 LEA 的比率可能会因种族/民族、地理位置和文化而变化高达两到三倍。糖尿病患者出现 DFU 和 LEA 的原因有很多，其中可能包括相互作用或其他原因。负责伤口修复的内在途径的改变、感染的存在、免疫的变化调节、神经病变、周围血管疾病、足部解剖功能的变化以及局部 DFU 是慢性伤口，顾名思义，就是未能遵循有序、有序的伤口。及时的顺序导致愈合并导致愈合受损。在 LEA 中，伤口愈合缓慢或根本不愈合，但为什么伤口会变成慢性尚不清楚。在过去的5年里，我们已经开发出初步证据表明NOS1AP的遗传变异，它编码一种称为阉鸡的蛋白质，与 DFU 愈合受损、LEA 风险增加有关，以及循环内皮前体细胞数量的减少，这已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 NOS1AP 变异与愈合受损之间的关联并辨别功能性的证据阉鸡的 NOS1AP 遗传变异以及最终阉鸡对伤口修复的影响的基础。我们目前研究的目的是探讨 NOS1AP 的常见遗传变异在这些人中的可能性患有糖尿病的人与伤口修复的改变有关。