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Department of Pharmacology and Center of Lung and Vascular Biology, The University of Illinois College of Medicine, Chicago, Illinois
The microvascular endothelial cell monolayer localized at the critical interface between the blood and vessel wall has the vital functions of regulating tissue fluid balance and supplying the essential nutrients needed for the survival of the organism. The endothelial cell is an exquisite "sensor" that responds to diverse signals generated in the blood, subendothelium, and interacting cells. The endothelial cell is able to dynamically regulate its paracellular and transcellular pathways for transport of plasma proteins, solutes, and liquid. The semipermeable characteristic of the endothelium (which distinguishes it from the epithelium) is crucial for establishing the transendothelial protein gradient (the colloid osmotic gradient) required for tissue fluid homeostasis. Interendothelial junctions comprise a complex array of proteins in series with the extracellular matrix constituents and serve to limit the transport of albumin and other plasma proteins by the paracellular pathway. This pathway is highly regulated by the activation of specific extrinsic and intrinsic signaling pathways. Recent evidence has also highlighted the importance of the heretofore enigmatic transcellular pathway in mediating albumin transport via transcytosis. Caveolae, the vesicular carriers filled with receptor-bound and unbound free solutes, have been shown to shuttle between the vascular and extravascular spaces depositing their contents outside the cell. This review summarizes and analyzes the recent data from genetic, physiological, cellular, and morphological studies that have addressed the signaling mechanisms involved in the regulation of both the paracellular and transcellular transport pathways.
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D. A. Buchner, F. Su, J. S. Yamaoka, M. Kamei, J. A. Shavit, L. K. Barthel, B. McGee, J. D. Amigo, S. Kim, A. W. Hanosh, et al. From the Cover: pak2a mutations cause cerebral hemorrhage in redhead zebrafish PNAS, August 28, 2007; 104(35): 13996 - 14001. [Abstract] [Full Text] [PDF]
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G. P. van Nieuw Amerongen and V. W.M. van Hinsbergh Endogenous RhoA Inhibitor Protects Endothelial Barrier Circ. Res., July 6, 2007; 101(1): 7 - 9. [Full Text] [PDF]
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M. Gorovoy, R. Neamu, J. Niu, S. Vogel, D. Predescu, J. Miyoshi, Y. Takai, V. Kini, D. Mehta, A. B. Malik, et al. RhoGDI-1 Modulation of the Activity of Monomeric RhoGTPase RhoA Regulates Endothelial Barrier Function in Mouse Lungs Circ. Res., July 6, 2007; 101(1): 50 - 58. [Abstract] [Full Text] [PDF]
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R. Scalia, Y. Gong, B. Berzins, L. J. Zhao, and K. Sharma Hyperglycemia Is a Major Determinant of Albumin Permeability in Diabetic Microcirculation: The Role of {micro}-Calpain Diabetes, July 1, 2007; 56(7): 1842 - 1849. [Abstract] [Full Text] [PDF]
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A. A. Birukova, I. Malyukova, V. Poroyko, and K. G. Birukov Paxillin-beta-catenin interactions are involved in Rac/Cdc42-mediated endothelial barrier-protective response to oxidized phospholipids Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L199 - L211. [Abstract] [Full Text] [PDF]
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M. J. Lorenowicz, M. Fernandez-Borja, and P. L. Hordijk cAMP Signaling in Leukocyte Transendothelial Migration Arterioscler. Thromb. Vasc. Biol., May 1, 2007; 27(5): 1014 - 1022. [Abstract] [Full Text] [PDF]
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A. A. Birukova, P. Fu, S. Chatchavalvanich, D. Burdette, O. Oskolkova, V. N. Bochkov, and K. G. Birukov Polar head groups are important for barrier-protective effects of oxidized phospholipids on pulmonary endothelium Am J Physiol Lung Cell Mol Physiol, April 1, 2007; 292(4): L924 - L935. [Abstract] [Full Text] [PDF]
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I. Singh, N. Knezevic, G. U. Ahmmed, V. Kini, A. B. Malik, and D. Mehta G{alpha}q-TRPC6-mediated Ca2+ Entry Induces RhoA Activation and Resultant Endothelial Cell Shape Change in Response to Thrombin J. Biol. Chem., March 16, 2007; 282(11): 7833 - 7843. [Abstract] [Full Text] [PDF]
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