Spatial variations in endothelial barrier function in disturbed flows in vitro.

Hindered barrier function has been implicated in the initiation and progression of atherosclerosis, a disease of focal nature associated with altered hemodynamics. In this study, endothelial permeability to macromolecules and endothelial electrical resistance were investigated in vitro in monolayers exposed to disturbed flow fields that model spatial variations in fluid shear stress found at arterial bifurcations. After 5 h of flow, areas of high shear stress gradients showed a 5.5-fold increase in transendothelial transport of dextran (molecular weight 70,000) compared with no-flow controls. Areas of undisturbed fully developed flow, within the same monolayer, showed a 2.9-fold increase. Monolayer electrical resistance decreased with exposure to flow. The resistance measured during flow and the rate of change in monolayer resistance after removal of flow were lowest in the vicinity of flow reattachment (highest shear stress gradients). These results demonstrate that endothelial barrier function and permeability to macromolecules are regulated by spatial variations in shear stress forces in vitro.

[1]  J. Cooper,et al.  Measurement of albumin permeability across endothelial monolayers in vitro. , 1987, Journal of applied physiology.

[2]  F. Minnear,et al.  Protein, not adenosine or adenine nucleotides, mediates platelet decrease in endothelial permeability. , 1997, American journal of physiology. Heart and circulatory physiology.

[3]  D. Newman,et al.  Influence of experimental stenosis on uptake of albumin by the abdominal aorta. , 1977, Atherosclerosis.

[4]  J A Frangos,et al.  Shear stress increases hydraulic conductivity of cultured endothelial monolayers. , 1995, The American journal of physiology.

[5]  A. Malik,et al.  Electrical method for detection of endothelial cell shape change in real time: assessment of endothelial barrier function. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[6]  A. Verin,et al.  Mechanisms of ionomycin-induced endothelial cell barrier dysfunction. , 1997, The American journal of physiology.

[7]  Ivar Giaever,et al.  Use of Electric Fields to Monitor the Dynamical Aspect of Cell Behavior in Tissue Culture , 1986, IEEE Transactions on Biomedical Engineering.

[8]  Van C. Mow,et al.  Cell Mechanics and Cellular Engineering , 2011, Springer New York.

[9]  M. Baetscher,et al.  An in vitro system for measuring endothelial permeability under hydrostatic pressure. , 1983, Experimental cell research.

[10]  K. Jan,et al.  Role of dying endothelial cells in transendothelial macromolecular transport. , 1990, Arteriosclerosis.

[11]  G. Truskey,et al.  Measurement of endothelial permeability to 125I-low density lipoproteins in rabbit arteries by use of en face preparations. , 1992, Circulation research.

[12]  H. Davies,et al.  Permeability of human venous endothelial cell monolayers perfused in microcarrier cultures: Effects of flow rate, thrombin, and cytochalasin D , 1991, Journal of cellular physiology.

[13]  M. Gimbrone,et al.  Vascular endothelium responds to fluid shear stress gradients. , 1992, Arteriosclerosis and thrombosis : a journal of vascular biology.

[14]  N Harbeck,et al.  Spatial and temporal regulation of gap junction connexin43 in vascular endothelial cells exposed to controlled disturbed flows in vitro. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[15]  C F Dewey,et al.  Shear stress gradients remodel endothelial monolayers in vitro via a cell proliferation-migration-loss cycle. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[16]  M. Edwards,et al.  Mechanisms of α‐thrombin, histamine, and bradykinin induced endothelial permeability , 1996 .

[17]  E. Salzman.  Progress in Hemostasis and Thrombosis , 1981 .

[18]  A. Barakat,et al.  Topographical mapping of sites of enhanced HRP permeability in the normal rabbit aorta. , 1992, Journal of Biomechanical Engineering.

[19]  K. Ookawa,et al.  Effects of Shear Stress on Cytoskeletal Structure and Physiological Functions of Cultured Endothelial Cells , 1994 .

[20]  M. Gimbrone.  Culture of vascular endothelium. , 1976, Progress in hemostasis and thrombosis.

[21]  T. Carew,et al.  Initiation of atherosclerotic lesions in cholesterol-fed rabbits. II. Selective retention of LDL vs. selective increases in LDL permeability in susceptible sites of arteries. , 1989, Arteriosclerosis.

[22]  L. McIntire,et al.  Permeability of human endothelial monolayers: effect of vasoactive agonists and cAMP. , 1989, Journal of applied physiology.

[23]  P. Davies.  How Do Vascular Endothelial Cells Respond to Flow , 1989 .

[24]  T. Sundqvist,et al.  Effects of hydrogen peroxide and phorbol myristate acetate on endothelial transport and F-actin distribution. , 1995, Experimental cell research.

[25]  A. Fishman,et al.  Permeability characteristics of cultured endothelial cell monolayers. , 1988, Journal of applied physiology.

[26]  C. M. Waters,et al.  Flow‐induced modulation of the permeability of endothelial cells cultured on microcarrier beads , 1996, Journal of cellular physiology.

[27]  J. Tarbell,et al.  Endothelial albumin permeability is shear dependent, time dependent, and reversible. , 1991, The American journal of physiology.

[28]  I. Giaever,et al.  Micromotion of mammalian cells measured electrically. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[29]  S. Weinbaum,et al.  Enhanced macromolecular permeability of aortic endothelial cells in association with mitosis. , 1988, Atherosclerosis.

[30]  A. Gotlieb,et al.  Patterns of Endothelial Microfilament Distribution in the Rabbit Aorta In Situ , 1989, Circulation research.

[31]  S. Weinbaum,et al.  Effect of cell turnover and leaky junctions on arterial macromolecular transport. , 1985, The American journal of physiology.