SHEAR STRESS EFFECTS ON ENDOTHELIAL TRANSPORT
剪切应力对内皮运输的影响
基本信息
- 批准号:2771536
- 负责人:
- 金额:$ 16.48万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1997
- 资助国家:美国
- 起止时间:1997-09-01 至 2000-08-31
- 项目状态:已结题
- 来源:
- 关键词:G protein aorta biological fluid transport cell membrane cow electron microscopy fluorescence microscopy gap junctions glycoproteins immunofluorescence technique intermediate filaments mechanical stress membrane transport proteins microfilaments microtubules receptor coupling second messengers tissue /cell culture vascular endothelium permeability
项目摘要
DESCRIPTION: (Adapted from the applicant's abstract) The endothelial cell
layer (EC) which lines blood vessel walls from the aorta to the capillaries
provides the principal barrier to transport of water and solutes between
blood and underlying tissue. ECs are continuously exposed to the mechanical
shearing force (shear stress) imposed by flowing blood on their surface. We
have shown recently that shear stress has an acute effect on transport
properties of EC layers in a well defined cell culture model, and this has
been confirmed in different vessels of live animals. Shear-dependent EC
transport has important implications for the function of normal
microvessels, which must deliver material to tissue in proportion to blood
flow in the region of demand. In arteries, shear dependent permeability of
macromolecules such as low density lipoprotein has been hypothesized to play
a key role in the localization of atherosclerotic lesions. Because of its
physiological significance, we propose to use a well-established cell
culture model in an engineered shearing device to study the phenomena of
shear-dependent EC transport. The specific aims of the proposed research
are: 1) To determine the effect of steady and oscillatory shear stress on
the hydraulic conductivity (Lp) and macromolecular permeability (Pe) of
bovine aortic endothelial cell (BAEC) monolayers. A unique apparatus will
be used which allows well-defined steady or oscillatory shear stress to be
imposed on BAEC monolayers grown to confluence on porous, polycarbonate
filters while Lp and Pe are measured simultaneously. 2) To determine the
physical transport pathways that are affected by shear stress, using four
techniques: (i) en face fluorescence microscopy to detect the presence of
endothelial gaps or leaky interendothelial junctions, (ii)
immunofluorescence labeling for ZO-1 protein to determine the status of
tight junctions, (iii) electron microscopic observation of colloidal
gold-labeled tracers to assess vesicular transport versus paracellular
transport, and (iv) partial pronase digestion of the EC glycocalyx to probe
the contribution of EC surface glycoproteins to transport barrier function
and its shear response. 3) To determine the biochemical mechanism(s)
mediating the shear-dependent response of EC transport properties. The role
of important second messengers systems (cAMP, cGMP, Ca++) coupled to the
plasma membrane through G-protein-dependent receptors will be probed with
various inhibitors and other modulators to manipulate the shear-dependent
response of EC transport. The role of the cytoskeleton will be assessed
with specific agents which disrupt the three major components:
microfilaments, micro tubules and intermediate filaments.
描述:(改编自申请人摘要)内皮细胞
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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JOHN M TARBELL其他文献
JOHN M TARBELL的其他文献
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{{ truncateString('JOHN M TARBELL', 18)}}的其他基金
The Endothelial Glycocalyx: Its Structure and Function and as a Mechanotransducer
内皮糖萼:其结构和功能以及作为机械传感器
- 批准号:
7887862 - 财政年份:2010
- 资助金额:
$ 16.48万 - 项目类别:
The Endothelial Glycocalyx: Its Structure and Function and as a Mechanotransducer
内皮糖萼:其结构和功能以及作为机械传感器
- 批准号:
8289879 - 财政年份:2010
- 资助金额:
$ 16.48万 - 项目类别:
The Endothelial Glycocalyx: Its Structure and Function and as a Mechanotransducer
内皮糖萼:其结构和功能以及作为机械传感器
- 批准号:
8247713 - 财政年份:2010
- 资助金额:
$ 16.48万 - 项目类别:
The Endothelial Glycocalyx: Its Structure and Function and as a Mechanotransducer
内皮糖萼:其结构和功能以及作为机械传感器
- 批准号:
8056011 - 财政年份:2010
- 资助金额:
$ 16.48万 - 项目类别:
The Endothelial Glycocalyx: Its Structure and Function and as a Mechanotransducer
内皮糖萼:其结构和功能以及作为机械传感器
- 批准号:
8452129 - 财政年份:2010
- 资助金额:
$ 16.48万 - 项目类别:
The Endothelial Glycocalyx: Its Structure and Function and as a Mechanotransducer
内皮糖萼:其结构和功能以及作为机械传感器
- 批准号:
8825611 - 财政年份:2010
- 资助金额:
$ 16.48万 - 项目类别:
Hemodynamic Forces Affect Endothelial Cell Pheotype in Arterial Disease
血流动力学影响动脉疾病中的内皮细胞表型
- 批准号:
7610927 - 财政年份:2008
- 资助金额:
$ 16.48万 - 项目类别:
Hemodynamic Forces Affect Endothelial Cell Pheotype in Arterial Disease
血流动力学影响动脉疾病中的内皮细胞表型
- 批准号:
7464627 - 财政年份:2008
- 资助金额:
$ 16.48万 - 项目类别:
Hemodynamic Forces Affect Endothelial Cell Pheotype in Arterial Disease
血流动力学影响动脉疾病中的内皮细胞表型
- 批准号:
7788858 - 财政年份:2008
- 资助金额:
$ 16.48万 - 项目类别:
CCNY/MSKCC Biomedical Engineering Partnership
CCNY/MSKCC 生物医学工程合作伙伴
- 批准号:
7128549 - 财政年份:2005
- 资助金额:
$ 16.48万 - 项目类别:
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