The shear stress of flowing blood on endothelial cells lining blood vessels and associated mass transport are important in the acute modulation of vascular tone, chronic remodeling of the vessel wall, and localization of atherosclerosis. Knowledge of in vivo wall shear stresses in curved and branched arteries under physiological conditions is limited by the inadequate spatial resolution of available blood flow diagnostic techniques. Thus, one of the broad objectives of the proposed research is to determine the magnitude and spatial distribution of wall shear stress and solute mass flux in complex arterial geometries under realistic physiological flow conditions. Interstitial fluid flow arises from the pressure gradient across the vessel wall. This flow exposes medial smooth muscle cells to shear stresses of the same order of magnitude as shear stresses on endothelial cells. The second broad objective of the proposed research is to improve estimates of interstitial flow shear stress and mass flux and extend understanding of the physiological response of smooth muscle cells to shear stress.
The specific aims of the proposed research are: 1) to measure wall shear rate in elastic curved and branch artery models with non-Newtonian blood analog fluids under physiological flow conditions simulating normal and vasoactive drug altered states; 2) to compute wall shear stress and mass flux distributions in curved and branch arteries with high spatial resolution; 3) to simulate interstitial fluid flow driven by the transmural pressure gradient and compute the associated shear stress and mass flux on smooth muscle cell surfaces; and 4) to determine the biochemical response of vascular smooth muscle cells to physiological levels of shear stress.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL035549-13
Application #
2713995
Study Section
Special Emphasis Panel (ZRG7-SAT (M1))
Project Start
1985-12-01
Project End
2000-05-30
Budget Start
1998-06-01
Budget End
1999-05-31
Support Year
13
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
City
University Park
State
PA
Country
United States
Zip Code
16802
Qazi, Henry; Palomino, Rocio; Shi, Zhong-Dong et al. (2013) Cancer cell glycocalyx mediates mechanotransduction and flow-regulated invasion. Integr Biol (Camb) 5:1334-43
Qazi, Henry; Shi, Zhong-Dong; Tarbell, John M (2011) Fluid shear stress regulates the invasive potential of glioma cells via modulation of migratory activity and matrix metalloproteinase expression. PLoS One 6:e20348
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Shi, Zhong-Dong; Ji, Xin-Ying; Qazi, Henry et al. (2009) Interstitial flow promotes vascular fibroblast, myofibroblast, and smooth muscle cell motility in 3-D collagen I via upregulation of MMP-1. Am J Physiol Heart Circ Physiol 297:H1225-34
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Dancu, Michael B; Berardi, Danielle E; Vanden Heuvel, John P et al. (2007) Atherogenic Endothelial Cell eNOS and ET-1 Responses to Asynchronous Hemodynamics are Mitigated by Conjugated Linoleic Acid. Ann Biomed Eng 35:1111-9
Garanich, Jeffrey S; Mathura, Rishi A; Shi, Zhong-Dong et al. (2007) Effects of fluid shear stress on adventitial fibroblast migration: implications for flow-mediated mechanisms of arterialization and intimal hyperplasia. Am J Physiol Heart Circ Physiol 292:H3128-35
Dancu, Michael B; Tarbell, John M (2006) Large Negative Stress Phase Angle (SPA) attenuates nitric oxide production in bovine aortic endothelial cells. J Biomech Eng 128:329-34

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