The structural and functional alterations of vascular endothelium caused by fluid shear stress will be investigated in vitro using cultured endothelial cells and a special apparatus we have developed for producing controlled fluid shear stress. The apparatus utilizes a shallow cone rotating above a flat plate to produce shear stresses between 10 to the -2 and 200 dynes/cm2; both laminar and turbulent flow conditions can be checked. Additional modifications will provide oscillating and alternating shear stress levels to investigate the response of the cells to shear conditions approximating those existing in vivo. Specific parameters of endothelial structure and function to be measured include: growth patterns and growth kinetics; migration and mitosis following injury; cell orientation and morphology; rates and mechanisms of endocytosis; cytoskeletal organization; and interaction with extracellular matrix. This is a collaborative research effort that draws upon the resources, expertise, and experience of the Fluid Mechanics Laboratory, Massachusetts Institute of Technology and the Vascular Pathophysiology Laboratory, Brigham and Women's Hospital. The research system to be used in this program, comprised of an accurately controlled fluid shear stress apparatus and well defined cultured endothelial specimens, should yield valuable information on the influence of fluid shear stress on the structure and function of vascular endothelium. Such information would provide new insights into vascular physiology and the pathogenesis of vascular diseases such as atherosclerosis.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL025536-06
Application #
3338119
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1980-04-01
Project End
1988-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Type
DUNS #
City
Cambridge
State
MA
Country
United States
Zip Code
Shen, J; Luscinskas, F W; Gimbrone Jr, M A et al. (1994) Fluid flow modulates vascular endothelial cytosolic calcium responses to adenine nucleotides. Microcirculation 1:67-78
Resnick, N; Collins, T; Atkinson, W et al. (1993) Platelet-derived growth factor B chain promoter contains a cis-acting fluid shear-stress-responsive element. Proc Natl Acad Sci U S A 90:4591-5
Shen, J; Gimbrone Jr, M A; Luscinskas, F W et al. (1993) Regulation of adenine nucleotide concentration at endothelium-fluid interface by viscous shear flow. Biophys J 64:1323-30
DePaola, N; Gimbrone Jr, M A; Davies, P F et al. (1992) Vascular endothelium responds to fluid shear stress gradients. Arterioscler Thromb 12:1254-7
Shen, J; Luscinskas, F W; Connolly, A et al. (1992) Fluid shear stress modulates cytosolic free calcium in vascular endothelial cells. Am J Physiol 262:C384-90
Muller, W A; Gimbrone Jr, M A (1986) Plasmalemmal proteins of cultured vascular endothelial cells exhibit apical-basal polarity: analysis by surface-selective iodination. J Cell Biol 103:2389-402
Davies, P F; Remuzzi, A; Gordon, E J et al. (1986) Turbulent fluid shear stress induces vascular endothelial cell turnover in vitro. Proc Natl Acad Sci U S A 83:2114-7