转基因/基因敲除动物心肌血管生成机制-猫眼课题宝

转基因/基因敲除动物心肌血管生成机制

批准号：

7433127

负责人：

NILANJANA MAULIK

金额：

$35.93万

依托单位：

UNIVERSITY OF CONNECTICUT SCH OF MED/DNT

依托单位国家：

美国

项目类别：

财政年份：

2006

资助国家：

美国

项目状态：

已结题

起止时间：

2006-06-15 至 2011-05-31

来源：

https://reporter.nih.gov/project-details/7433127

关键词：

4-ethoxymethylene-2-phenyl-2-oxazoline-5-one Address Angiogenesis Inhibitors Angiogenic Factor Antigen-Antibody Complex Apoptosis Apoptotic Area Arteries Binding Biological Assay Biological Process Blood Vessels Blood capillaries Blood flow Candidate Disease Gene Cardiac Cardiac Death Cardiac Myocytes Cell Survival Chronic Clinical Collagen Collateral Circulation Complex Coronary Coronary artery DNA Binding Development Disease Disruption Down-Regulation Drug Delivery Systems Endothelial Cells Enhancers Event Experimental Models Exposure to Face Family Gelshift Analysis Gene Chips Gene Targeting Generations Genes Genetic Genetically Engineered Mouse Genomics Glycogen Synthase Kinases Growth Growth Factor Grx1 protein Hand Health Heart Human Hypoxia In Situ Nick-End Labeling In Vitro Infarction Injury Ischemia Ischemic Preconditioning Knock-out Knockout Mice Laboratories Limb structure Loa Measures Mediating Methodology Mitogens Modality Modeling Molecular Molecular Biology Techniques Molecular Weight Mus Muscle Cells Myocardial Myocardial Infarction Myocardial Ischemia Myocardium NAD(P)H oxidase Necrosis Nuclear Translocation Oxidation-Reduction Oxidative Stress Pathway interactions Pattern Personal Satisfaction Phase Phosphorylation Phosphotransferases Physiological Processes Physiological reperfusion Physiology Play Porifera Principal Investigator Process Protein Overexpression Proteins Proto-Oncogene Proteins c-akt Protocols documentation Rattus Reactive Oxygen Species Readiness Receptor Protein-Tyrosine Kinases Regulation Relative (related person)Reperfusion Therapy Reporting Research Research Design Research Personnel Reverse Transcriptase Polymerase Chain Reaction Role SP1 gene SRC gene Signal Pathway Signal Transduction Signal Transduction Pathway Small Interfering RNA Staining method Stains Stimulus Stream Stress System TCF Transcription Factor Techniques Testing Therapeutic Thinking Thioredoxin Time Tissues Transgenic Model Transgenic Organisms Vascular Endothelial Growth Factor Receptor-1 Vascular Endothelial Growth Factor Receptor-2 Vascular Endothelial Growth Factors Vascular Endothelium Vascular Permeabilities Vascular blood supply Ventricular Ventricular Function Western Blotting Wound Healing angiogenesis artery occlusion bench to bedside beta catenin capillary clinically relevant cytokine density gene therapy glutaredoxin glycogen synthase kinase 3 beta heart function heme oxygenase-1 in vivo insight interdisciplinary approach interest knock-down knockout animal knockout gene neovascularization neutrophil cytosol factor 67K novel prevent programs protein expression rac GTP-Binding Proteins receptor response restoration size therapeutic target transcription factor

项目摘要

项目成果

NILANJANA MAULIK的其他基金

相似基金

相关文献

中文摘要

翻译

点击翻译按钮获取中文摘要

英文摘要

DESCRIPTION (provided by applicant): Neovascularization, the natural physiological process of formation of new blood vessels, is extremely important to ameliorate the function of the heart that undergoes ischemic stress. This process is potentially important for the treatment of ischemic heart and limb ischemia which includes formation of capillaries (angiogenesis) and collateral arteries. We demonstrated that ischemic preconditioning (IP) of the heart can trigger angiogenesis. Reactive oxygen species (ROS) derived from gp91phox (Nox2)-containing NAD(P)H oxidase is found to be involved in angiogenic process which involves vascular endothelial growth factor (VEGF) signaling. The role of gp91phox-derived ROS in neovascularization in response to tissue ischemia is unknown. Again to determine this redox signaling we will examine the involvement of principal redox regulated genes, thioredoxin and glutaredoxin in the IP hearts. Discerning the myriad pathways that are possibly associated with this vascular growth process is therefore of utmost importance to develop targeted drugs and bring the therapy from bench to bedside. Previous studies, including ours, also have shown that transient ischemia upregulates VEGF protein in cardiac tissues. Thus, this study will attempt to address an important clinical issue by identifying potential candidates of VEGF signaling in several gene knockout animals such as Flk-1+/-, Flt-1+/-, gp-91 phox-/-, HO-1+/+, Trx-1+/+, Grx1+/+, Grx1-/-. This study will utilize a broad multidisciplinary approach that will combine various techniques, including latest molecular biology techniques, physiology and gene targeting. Aim 1. Activation and molecular mechanism of the GSK-3beta phosphorylation and beta-catenin translocation followed by pro-angiogenic molecule VEGF expression will be investigated. Aim 2. Genetically-engineered mice will be used such as MK2-/- to identify down stream target candidates of VEGF signaling through its receptors in IP as well as ischemic reperfused myocardium in vivo Aim 3. ROS mediated stress plays significant role in VEGF induced angiogenesis through Trx and Grx protein. Aim 4.To gain insights into the mechanisms and to identify candidate genes involved in VEGF- NAD(P)H oxidase signaling in gp91phox-/- homozygous mice we will use Affymetrix Gene chip Analysis. This proposal will provide and will identify important new insights into the cellular and molecular mechanisms of the cardioprotection provided by VEGF signaling through important candidate genes.

期刊论文(0)

专著(0)

科研奖励(0)

会议论文