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

The morphogenetic regulation of cardiac valves by fluid flow.

流体流动对心脏瓣膜的形态发生调节。

基本信息

批准号：
8075038
负责人：
JAY D POTTS
金额：
$ 10.04万
依托单位：
UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-08-01 至 2013-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8075038
关键词：
3-Dimensional Affect Atomic Force Microscopy Biochemical Biological Biological Assay Biological Models Biomedical Engineering Cardiac Cardiac conduction system Cardiovascular system Cells Collagen Complex Congenital Abnormality Congenital Heart Defects Data Development Environment Event Exposure to Extracellular Matrix Proteins Funding Gene Expression Gene Expression Regulation Genes Goals Grant Heart Heart Valves Independent Scientist Award Knockout Mice Knowledge Laboratories Mechanics Methods Modeling Molecular Monitor Morphogenesis Morphology Mus National Heart, Lung, and Blood Institute Pathway interactions Play Principal Investigator Process Property Regulation Research Research Personnel Rheology Role Signal Pathway Signal Transduction Staging Structural Protein System Techniques Testing Time Tissue Engineering Tissues Tube abstracting congenital heart disorder design fluid flow gene therapy programs protein expression research study response scaffold treatment strategy

项目摘要

DESCRIPTION (provided by applicant): The goal of this KO2 proposal is to allow the Principal Investigator to understand the role that fluid flow has on regulating key gene that control the morphology of developing heart valves, providing him with greater than 75% of time dedicated to his research over the next five years. Fluid flow has shown to be crucial for cardiac form and :unction. Alterations in fluid flow leads to various cardiac malformations including the cardiac valves. Specifically the Principal Investigator will focus on elucidating the effects that various flow parameters have on the morphology and gene regulation of key molecules in a unique 3-D model system established in the investigators laboratory. He will try to establish the mechanism that flow activates and where in the cascade of crucial signaling events fluid flow should be placed. The long term goal is to understand the importance of fluid flow n regulating the morphology of the developing cardiac valves. The knowledge gained from these experiments will create new strategies for the treatment of cardiac birth defects and valuable information concerning the design of tissue-engineered heart valves. A range of biochemical and cell biological studies on signaling mechanisms crucial to valve development are funded by NHLBI RO1 grant (HL072958-01). Stimulated by a new model system developed in the Pi's laboratory to study later stages of valve development which is amenable to directly studying the effect of fluid flow on valve formation, the Principal Investigator would like to expand the project to investigate this crucial question. The specific aims will test the hypothesis: that fluid flow in the heart regulates valvular morphogenetics and involves key signaling pathways. Our tenets will be tested in the following aims: 1) Determine the consequence of fluid flow on the differentiation and morphogenesis of valve leaflets; 2) Identification of altered expression of structural proteins in the Jak-3 deficient developing valves under flow; 3) Characterization of altered gene expression in endocardial cells exposed to fluid flow. As part of the KO2 project new. techniques will be introduced into the investigators already interdisciplinary laboratory. The Principal Investigator will undergo additional exposure to Rheology (study of fluid flow) and interactions with bioengineers and cardiovascular biologists will be expanded. The investigator has assembled a unique and dynamic group of investigators from which to draw upon. The Principal Investigator is well versed to answer truly fundamental questions regarding the role of fluid flow in regulating cardiac valve formation (End of Abstract)

描述（由申请人提供）：

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A 3-D cardiac muscle construct for exploring adult marrow stem cell based myocardial regeneration.

用于探索基于成体骨髓干细胞的心肌再生的 3-D 心肌结构。

DOI：
10.1016/j.biomaterials.2010.01.041
发表时间：
2010
期刊：
Biomaterials
影响因子：
14
作者：
Valarmathi,ManiT;Goodwin,RichardL;Fuseler,JohnW;Davis,JeffreyM;Yost,MichaelJ;Potts,JayD
通讯作者：
Potts,JayD

Regulation of osteogenic differentiation of rat bone marrow stromal cells on 2D nanorod substrates.