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Apoptotic Signaling Induces Hyperpermeability Following Hemorrhagic Shock

凋亡信号传导导致失血性休克后通透性过高

基本信息

批准号：
7291594
负责人：
ED W CHILDS
金额：
$ 13.61万
依托单位：
SCOTT AND WHITE MEMORIAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-25 至 2011-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7291594
关键词：
Acute Address Adherence Adherens Junction Adhesives Age American Heart Association Animal Model Apoptosis Apoptotic Area Atomic Force Microscopy Attenuated Award Basement membrane Biology Blood Circulation Blood Vessels Burn Trauma Cardiogenic Shock Cardiovascular Physiology Cardiovascular system Caspase Cause of Death Cell Communication Cell Death Cells Cellular biology Cessation of life Cleaved cell Clinical Complement Complex Condition Data Development Drug Delivery Systems Edema Endothelial Cells Environment Face Functional disorder Funding Goals Grant Hand Hemorrhagic Shock Homeostasis Injury Institution Interdisciplinary Study Intervention Investigation Ischemia Journals Laboratories Liquid substance Lung Mediator of activation protein Mentored Research Scientist Development Award Mitochondria Modeling Modification Molecular Biology Nervous system structure Neurology Organ Pathway interactions Permeability Proteins Range Regulation Research Research Design Research Personnel Sepsis Shock Signal Transduction Site Stimulus Structure Techniques Testing Therapeutic Tissues Transfection Trauma United States National Institutes of Health Vascular Permeabilities Work abstracting base cadherin 5 caspase-3 concept design experience in vivo innovation insight interstitial intravital microscopy monolayer novel pressure prevent programs research study skills statistics symposium

项目摘要

DESCRIPTION (provided by applicant): This application describes a comprehensive vascular research program designed to develop Dr. Childs into an independent investigator. Through course work in molecular biology, research design, and statistics, he will acquire the necessary analytical skills to achieve this goal. He will also be required to attend several annual conferences and a monthly journal club. An Advisory Board of experienced investigators in vascular and cellular biology has been established for Dr. Childs to obtain hands on experience in laboratory techniques. Development of grantsmanship is emphasized throughout the duration of the K01 award, beginning with applications for local funds, graduating to an American Heart Association grant, and culminating in a R01 submission to the NIH in the third year of this award. The research plan focuses on the regulation of endothelial cell-cell adherens junctions to prevent microvascular hyperpermeability following hemorrhagic shock. Fluid loss from the circulation is a major factor in compromising cardiovascular homeostasis following trauma, burns, sepsis and hemorrhagic shock. Preventing microvascular barrier opening or reestablishing barrier function is crucial in limiting the deleterious effects on the cardiovascular, pulmonary and nervous systems. Hemorrhagic shock-induced hyperpermeability results in alteration of the endothelial cell-cell adherens junction complex. Site-specific alterations in the structure of (3-catenin have been implicated as an important modulator of these junctions. The applicant hypothesizes that hemorrhagic shock-induced activation of caspases results in a (3- catenin-dependent modification of endothelial adherens junction. To address this hypothesis, the applicant proposes two interlocking specific aims: (1) define the relationship between the apoptotic cascade and hemorrhagic shock-induced hyperpermeability and (2) identify the interaction(s) of caspase-3 with the adherens junction complex. Intravital microscopy with a novel in vivo protein transfection technique in parallel with cell monolayers will be utilized to determine changes in microvascular hyperpermeability. Atomic force microscopy will be used to assess endothelial cell adhesive forces. (End of Abstract)

描述（由申请人提供）：