PALMITOYLATION DYNAMICS, DIABETES AND VASCULAR INTEGRITY

棕榈酰化动力学、糖尿病和血管完整性

基本信息

批准号：
9180999
负责人：
Xiaochao Wei
金额：
$ 19.06万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-15 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9180999
关键词：
Ablation Acylation Address Adhesions Animals Blood Vessels Cardiovascular Diseases Cardiovascular system Cells Complications of Diabetes Mellitus Defect Diabetes Mellitus Diabetic mouse Elderly Endarterectomy Endothelial Cells Enzymes Exploratory/Developmental Grant Functional disorder Future Genetic Goals Guanosine Triphosphate Health Hindlimb Homeostasis Human In Vitro Intercellular Junctions Ischemia Lead Limb structure Lipids Measures Mediating Membrane Metabolic Modification Mus Pathway interactions Patients Perfusion Peripheral arterial disease Process Protein S Proteins R-ras protein Research Role Signal Pathway Signal Transduction Specimen Streptozocin Vascular remodeling Vascularization abstracting angiogenesis base biobank cadherin 5 cell motility clinically relevant cohesion deacylation design diabetic diabetic cardiomyopathy diabetic patient femoral artery improved insight mouse model novel older patient overexpression palmitoylation protein function trafficking treatment strategy

项目摘要

Abstract Vascular complications in elderly people with diabetes continue to be major health problems throughout the world, yet lipid-associated mechanism for disrupting vascular integrity is unclear. As a major type of covalent lipid modifications, reversible protein S-palmitoylation has emerged as a potentially critical post-translational process in signaling pathway. Our studies suggest that the protein depalmitoylation enzyme APT1 is critical for ischemic vascular remodeling that is relevant to peripheral artery disease. By integrating in vitro studies, mouse models and patient specimen analysis, the research plan will lead to the identification and characterization of APT1-dependent R-Ras palmitoylation dynamics in vascular complications of diabetic patients. The result of the study will warrant the future focus on the role of lipid modification in pathophysiology and offer the promise of discovering novel targets for peripheral artery disease in elderly patient with diabetes.

抽象的糖尿病老年人的血管并发症在整个过程中仍然是主要的健康问题尚不清楚世界，但脂肪相关的机制尚不清楚。作为主要的共价类型脂质修饰，可逆蛋白S-膜酰化已成为一种潜在的关键后翻译后信号通路中的过程。我们的研究表明，蛋白质deplmitoylation酶APT1对于与周围动脉疾病有关的缺血性血管重塑。通过整合体外研究，小鼠模型和患者标本分析，研究计划将导致识别和表征糖尿病患者血管并发症中的APT1依赖性R-RAS棕榈酰化动力学。结果研究将保证将来关注脂质修饰在病理生理学中的作用，并提供的希望发现老年糖尿病患者外周动脉疾病的新靶标。