Abstract

The aim of this project is to establish the role of the rheological properties of blood cells in circulatory regulation in health and disease. The blood cell properties to be studied are the deformability of red blood cells (RBCs) and white blood cells (WBCs), RBC aggregation, WBC adhesion to vascular endothelium, and the concentration of RBCs and WBCs. Homologous blood cells with alteration in the above-mentioned properties will be administered either by isovolumetric exchange transfusion into the entire circulation or by perfusion into individual organs. The resulting changes in hemodynamic functions, oxygen transport and vascular permeability will be determined in vivo and correlated with the alterations in rheological properties of blood cells assessed by in vitro experiments and theoretical analysis. The results will be correlated with the changes in the molecular organization of membrane and the flow dynamics in microcirculation. The multidisciplinary approach is used to study the role of blood cell properties (RBC deformability, RBC aggregation, WBC deformability and WBC adhesion) on circulatory dynamics in terms of regional blood flow and oxygen delivery. The changes in blood flow and resistance will be analyzed by taking into account the neurohumoral factors which may affect the vascular hindrance, in addition to blood rheology. The ultimate aim is to elucidate the role of blood cell rheology in some of the pathophysiological mechanisms of hematological and circulatory diseases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37HL044147-07
Application #
2221348
Study Section
Special Emphasis Panel (NSS)
Project Start
1989-05-01
Project End
1999-04-30
Budget Start
1995-05-01
Budget End
1996-04-30
Support Year
7
Fiscal Year
1995
Total Cost
Indirect Cost

  Institution

Name
University of California San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093

  Publications

Chien, Shu (2003) Molecular and mechanical bases of focal lipid accumulation in arterial wall. Prog Biophys Mol Biol 83:131-51
Liu, Yi; Chen, Benjamin P-C; Lu, Min et al. (2002) Shear stress activation of SREBP1 in endothelial cells is mediated by integrins. Arterioscler Thromb Vasc Biol 22:76-81
Zhao, Y; Chien, S; Skalak, R et al. (2001) Leukocyte rolling in rat mesentery venules: distribution of adhesion bonds and the effects of cytoactive agents. Ann Biomed Eng 29:360-72
Shyy, J Y (2001) Mechanotransduction in endothelial responses to shear stress: review of work in Dr. Chien's laboratory. Biorheology 38:109-17
Jin, G; Chieh-Hsi Wu, J; Li, Y S et al. (2000) Effects of active and negative mutants of Ras on rat arterial neointima formation. J Surg Res 94:124-32
Jin, G; Sah, R L; Li, Y S et al. (2000) Biomechanical regulation of matrix metalloproteinase-9 in cultured chondrocytes. J Orthop Res 18:899-908
Chen, K D; Li, Y S; Kim, M et al. (1999) Mechanotransduction in response to shear stress. Roles of receptor tyrosine kinases, integrins, and Shc. J Biol Chem 274:18393-400
Artmann, G M; Kelemen, C; Porst, D et al. (1998) Temperature transitions of protein properties in human red blood cells. Biophys J 75:3179-83
Chien, S; Shyy, J Y (1998) Effects of hemodynamic forces on gene expression and signal transduction in endothelial cells. Biol Bull 194:390-1;discussion 392-3
Chien, S; Li, S; Shyy, Y J (1998) Effects of mechanical forces on signal transduction and gene expression in endothelial cells. Hypertension 31:162-9

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