权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Regulation of oxidative stress and vascular remodeling by EBP50

EBP50 对氧化应激和血管重塑的调节

基本信息

批准号：
9920603
负责人：
ALESSANDRO BISELLO
金额：
$ 34.31万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-10 至 2022-03-10
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9920603
关键词：
Adaptor Signaling Protein Antioxidants Arterial Injury Asses Atherosclerosis Binding Proteins Bite Blood Vessels Bone Marrow Transplantation Cardiovascular Diseases Cardiovascular system Cell model Cells Chronic Data Development Disease Endothelium Enzymes Event F Box Domain FOXO1A gene Foundations Foxes Generations Goals Hydrogen Hyperplasia Inflammation Inflammation Mediators Inflammatory Inflammatory Response Injury Intervention Mediating Mediator of activation protein Methods Mitochondria Molecular Morbidity - disease rate Mus NF-kappa B Names Nitric Oxide Oxidative Regulation Oxidative Stress Oxides Oxygen Partner in relationship Pathogenesis Pathogenicity Pathologic Pathology Pathway interactions Peroxonitrite Pharmacology Play Prevention Proteins Public Health Publishing Reactive Oxygen Species Regulation Research Role S Phase SOD2 gene Scaffolding Protein Signal Transduction Site Skp2 Proteins Smooth Muscle Myocytes Source Stimulus Stress Superoxides System Testing Time Vascular Diseases Vascular Smooth Muscle Vascular remodeling age related antioxidant enzyme base catalase cytokine design experimental study ezrin inhaled nitric oxide insight macrophage mitochondrial dysfunction mortality mouse model neointima formation new therapeutic target novel protein kinase P response restenosis stem transcription factor transplant model ubiquitin-protein ligase vascular inflammation

项目摘要

Chronic inflammation and oxidative stress are hallmarks of many age-related diseases, including cardiovascular disease. There is a critical need to establish the molecular and cellular basis for the increased and sustained inflammatory and oxidative status that leads to vascular disease. We have recently shown that the scaffolding protein Ezrin Binding Protein 50 (EBP50, also known as NHERF1) is a key regulator of systemic and vascular inflammation. Studies in mice and in cell systems show that inflammatory stimuli promote EBP50 expression in macrophages and vascular smooth muscle cells (VSMC) and, conversely, EBP50 increases inflammatory responses in these cells. Preliminary studies also indicate that EBP50 increases the generation of reactive oxygen species and potentiates oxidative stress in vessels. These findings suggest a novel and pathologically relevant role for EBP50 in the control of both inflammation and oxidative stress. We hypothesize that EBP50 promotes a chronic inflammatory and oxidative status that contributes to atherosclerosis and vascular disease. Three specific aims are designed to test this hypothesis and elucidate the molecular mechanisms underlying these novel actions of EBP50. In Aim 1 that molecular mechanisms by which EBP50 regulates oxidative stress will be elucidated. Aim 2 will determine the actions of EBP50 that regulate mitochondrial function and the responses to inflammatory and oxidative stimuli. In Aim 3, murine models will be used to determine the effect of EBP50 on neointima formation. This research plan employs complementary methods to define a novel mechanism by which EBP50 regulates inflammation and oxidative stress. The long-term goal is to identify and exploit novel avenues for pharmacological intervention aimed at limiting chronic inflammation and oxidative stress.

慢性炎症和氧化应激是许多与年龄有关的疾病的标志，包括