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The Endothelial Glycocalyx as a Barrier to Leukocyte Adhesion and Its Mediation by Extracellular Proteases

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Abstract

The endothelial cell (EC) surface is coated with a layer of polysaccharides linked to membrane-bound and trans-membrane proteoglycans that comprise the glycocalyx, which is augmented by adsorbed proteins derived from the blood stream. This surface layer has been shown to affect hemodynamics in small blood vessels of the microcirculation, the resistance to flow, and leukocyte (WBC) to EC adhesion. Parallel studies of WBC–EC adhesion in response to chemoattractants and cytokines, and shedding of constituents of the glycocalyx, have suggested a role for activation of extracellular proteases in mediating the dynamics of WBC adhesion in response to inflammatory and ischemic stimuli. Likely candidates among the many proteases present are the matrix metalloproteases (MMPs). Inhibition of MMP activation with sub-antimicrobial doses of doxycycline, or zinc chelators, has also inhibited WBC adhesion and shedding of glycans from the EC surface in response to the chemoattractant fMLP. Taken together, these studies suggest that shedding of the EC glycocalyx exposes adhesion receptors and thus enhances WBC–EC adhesion. Future therapeutic strategies for treating pathologies such as the low flow state and inflammation may benefit by further exploration of the mechanics of the glycocalyx in light of protease activation and shear-dependent effects.

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References

  1. Adamson, R. H., and G. Clough. Plasma proteins modify the endothelial cell glycocalyx of frog mesenteric microvessels. J. Physiol. 445:473–486, 1992.

    PubMed  CAS  Google Scholar 

  2. Alon, R., D. A. Hammer, and T. A. Springer. Lifetime of the P-selectin–carbohydrate bond and its response to tensile force in hydrodynamic flow. Nature 374:539–542, 1995.

    Article  PubMed  CAS  Google Scholar 

  3. Arfors, K. E., C. Lundberg, L. Lindbom, K. Lundberg, P. G. Beatty, and J. M. Harlan. A monoclonal antibody to the membrane glycoprotein complex CD18 inhibits polymorphonuclear leukocyte accumulation and plasma leakage in vivo. Blood 69:338–340, 1987.

    PubMed  CAS  Google Scholar 

  4. Arisaka, T., M. Mitsumata, M. Kawasumi, T. Tohjima, S. Hirose, and Y. Yoshida. Effects of shear stress on glycosaminoglycan synthesis in vascular endothelial cells. Ann. N. Y. Acad. Sci. 748:543–554, 1995.

    Article  PubMed  CAS  Google Scholar 

  5. Barabino, G. A., M. O. Platt, and D. K. Kaul. Sickle cell biomechanics. Annu. Rev. Biomed. Eng. 12:345–367, 2010.

    Article  PubMed  CAS  Google Scholar 

  6. Bennett, H. S., J. H. Luft, and J. C. Hampton. Morphological classifications of vertebrate blood capillaries. Am. J. Physiol. 196:381–390, 1959.

    PubMed  CAS  Google Scholar 

  7. Bruegger, D., M. Jacob, M. Rehm, M. Loetsch, U. Welsch, P. Conzen, and B. F. Becker. Atrial natriuretic peptide induces shedding of endothelial glycocalyx in coronary vascular bed of guinea pig hearts. Am. J. Physiol. Heart Circ. Physiol. 289:H1993–H1999, 2005.

    Article  PubMed  CAS  Google Scholar 

  8. Brule, S., N. Charnaux, A. Sutton, D. Ledoux, T. Chaigneau, L. Saffar, and L. Gattegno. The shedding of syndecan-4 and syndecan-1 from HeLa cells and human primary macrophages is accelerated by SDF-1/CXCL12 and mediated by the matrix metalloproteinase-9. Glycobiology 16:488–501, 2006.

    Article  PubMed  CAS  Google Scholar 

  9. Cabrales, P., B. Y. Vazquez, A. G. Tsai, and M. Intaglietta. Microvascular and capillary perfusion following glycocalyx degradation. J. Appl. Physiol. 102:2251–2259, 2007.

    Article  PubMed  Google Scholar 

  10. Chappell, D., K. Hofmann-Kiefer, M. Jacob, M. Rehm, J. Briegel, U. Welsch, P. Conzen, and B. F. Becker. TNF-alpha induced shedding of the endothelial glycocalyx is prevented by hydrocortisone and antithrombin. Basic Res. Cardiol. 104:78–89, 2009.

    Article  PubMed  CAS  Google Scholar 

  11. Chappell, D., M. Jacob, O. Paul, M. Rehm, U. Welsch, M. Stoeckelhuber, P. Conzen, and B. F. Becker. The glycocalyx of the human umbilical vein endothelial cell: an impressive structure ex vivo but not in culture. Circ. Res. 104:1313–1317, 2009.

    Article  PubMed  CAS  Google Scholar 

  12. Colburn, P., E. Kobayashi, and V. Buonassisi. Depleted level of heparan sulfate proteoglycan in the extracellular matrix of endothelial cell cultures exposed to endotoxin. J. Cell. Physiol. 159:121–130, 1994.

    Article  PubMed  CAS  Google Scholar 

  13. Constantinescu, A. A., H. Vink, and J. A. Spaan. Elevated capillary tube hematocrit reflects degradation of endothelial cell glycocalyx by oxidized LDL. Am. J. Physiol. Heart Circ. Physiol. 280:H1051–H1057, 2001.

    PubMed  CAS  Google Scholar 

  14. Constantinescu, A. A., H. Vink, and J. A. Spaan. Endothelial cell glycocalyx modulates immobilization of leukocytes at the endothelial surface. Arterioscler. Thromb. Vasc. Biol. 23:1541–1547, 2003.

    Article  PubMed  CAS  Google Scholar 

  15. Danielli, J. F. Capillary permeability and oedema in the perfused frog. J. Physiol. 98:109–129, 1940.

    PubMed  CAS  Google Scholar 

  16. DeLano, F. A., and G. W. Schmid-Schonbein. Proteinase activity and receptor cleavage: mechanism for insulin resistance in the spontaneously hypertensive rat. Hypertension 52:415–423, 2008.

    Article  PubMed  CAS  Google Scholar 

  17. Desjardins, C., and B. R. Duling. Heparinase treatment suggests a role for the endothelial cell glycocalyx in regulation of capillary hematocrit. Am. J. Physiol. 258:H647–H654, 1990.

    PubMed  CAS  Google Scholar 

  18. Ding, K., M. Lopez-Burks, J. A. Sanchez-Duran, M. Korc, and A. D. Lander. Growth factor-induced shedding of syndecan-1 confers glypican-1 dependence on mitogenic responses of cancer cells. J. Cell Biol. 171:729–738, 2005.

    Article  PubMed  CAS  Google Scholar 

  19. Endo, K., T. Takino, H. Miyamori, H. Kinsen, T. Yoshizaki, M. Furukawa, and H. Sato. Cleavage of syndecan-1 by membrane type matrix metalloproteinase-1 stimulates cell migration. J. Biol. Chem. 278:40764–40770, 2003.

    Article  PubMed  CAS  Google Scholar 

  20. Fahraeus, R. The suspension stability of blood. Physiol. Rev. 9:241–274, 1929.

    Google Scholar 

  21. Fitzgerald, M. L., Z. Wang, P. W. Park, G. Murphy, and M. Bernfield. Shedding of syndecan-1 and -4 ectodomains is regulated by multiple signaling pathways and mediated by a TIMP-3-sensitive metalloproteinase. J. Cell Biol. 148:811–824, 2000.

    Article  PubMed  CAS  Google Scholar 

  22. Fux, L., N. Ilan, R. D. Sanderson, and I. Vlodavsky. Heparanase: busy at the cell surface. Trends Biochem. Sci. 34:511–519, 2009.

    Article  PubMed  CAS  Google Scholar 

  23. Gao, L., and H. H. Lipowsky. Composition of the endothelial glycocalyx and its relation to its thickness and diffusion of small solutes. Microvasc. Res. 80:394–401, 2010.

    Article  PubMed  CAS  Google Scholar 

  24. Golub, L. M., H. M. Lee, M. E. Ryan, W. V. Giannobile, J. Payne, and T. Sorsa. Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mechanisms. Adv. Dent. Res. 12:12–26, 1998.

    Article  PubMed  CAS  Google Scholar 

  25. Gotte, M. Syndecans in inflammation. FASEB J. 17:575–591, 2003.

    Article  PubMed  CAS  Google Scholar 

  26. Gouverneur, M., J. A. Spaan, H. Pannekoek, R. D. Fontijn, and H. Vink. Fluid shear stress stimulates incorporation of hyaluronan into endothelial cell glycocalyx. Am. J. Physiol. Heart Circ. Physiol. 290:H458–H462, 2006.

    Article  PubMed  CAS  Google Scholar 

  27. Grimm, J., R. Keller, and P. G. de Groot. Laminar flow induces cell polarity and leads to rearrangement of proteoglycan metabolism in endothelial cells. Thromb. Haemost. 60:437–441, 1988.

    PubMed  CAS  Google Scholar 

  28. Gronski, Jr., T. J., R. L. Martin, D. K. Kobayashi, B. C. Walsh, M. C. Holman, M. Huber, H. E. Van Wart, and S. D. Shapiro. Hydrolysis of a broad spectrum of extracellular matrix proteins by human macrophage elastase. J. Biol. Chem. 272:12189–12194, 1997.

    Article  PubMed  CAS  Google Scholar 

  29. Haas, T. L., M. Milkiewicz, S. J. Davis, A. L. Zhou, S. Egginton, M. D. Brown, J. A. Madri, and O. Hudlicka. Matrix metalloproteinase activity is required for activity-induced angiogenesis in rat skeletal muscle. Am. J. Physiol. Heart Circ. Physiol. 279:1540–1547, 2000.

    Google Scholar 

  30. Hafezi-Moghadam, A., K. L. Thomas, A. J. Prorock, Y. Huo, and K. Ley. l-Selectin shedding regulates leukocyte recruitment. J. Exp. Med. 193:863–872, 2001.

    Article  PubMed  CAS  Google Scholar 

  31. Haldenby, K. A., D. C. Chappell, C. P. Winlove, K. H. Parker, and J. A. Firth. Focal and regional variations in the composition of the glycocalyx of large vessel endothelium. J. Vasc. Res. 31:2–9, 1994.

    PubMed  CAS  Google Scholar 

  32. Hayward, R., R. Scalia, B. Hopper, J. Z. Appel, III, and A. M. Lefer. Cellular mechanisms of heparinase III protection in rat traumatic shock. Am. J. Physiol. 275:H23–H30, 1998.

    PubMed  CAS  Google Scholar 

  33. Henry, C. B., and B. R. Duling. TNF-alpha increases entry of macromolecules into luminal endothelial cell glycocalyx. Am. J. Physiol. Heart Circ. Physiol. 279:H2815–H2823, 2000.

    PubMed  CAS  Google Scholar 

  34. Hofmann-Kiefer, K. F., G. I. Kemming, D. Chappell, M. Flondor, H. Kisch-Wedel, A. Hauser, S. Pallivathukal, P. Conzen, and M. Rehm. Serum heparan sulfate levels are elevated in endotoxemia. Eur. J. Med. Res. 14:526–531, 2009.

    PubMed  CAS  Google Scholar 

  35. Hoover, R. L., R. Folger, W. A. Haering, B. R. Ware, and M. J. Karnovsky. Adhesion of leukocytes to endothelium: roles of divalent cations, surface charge, chemotactic agents and substrate. J. Cell Sci. 45:73–86, 1980.

    PubMed  CAS  Google Scholar 

  36. House, S. D., and H. H. Lipowsky. Leukocyte–endothelium adhesion: microhemodynamics in mesentery of the cat. Microvasc. Res. 34:363–379, 1987.

    Article  PubMed  CAS  Google Scholar 

  37. House, S. D., and H. H. Lipowsky. Microvascular hematocrit and red cell flux in rat cremaster muscle. Am. J. Physiol. 252:H211–H222, 1987.

    PubMed  CAS  Google Scholar 

  38. Huxley, V. H., and F. E. Curry. Differential actions of albumin and plasma on capillary solute permeability. Am. J. Physiol. 260:H1645–H1654, 1991.

    PubMed  CAS  Google Scholar 

  39. Ihrcke, N. S., and J. L. Platt. Shedding of heparan sulfate proteoglycan by stimulated endothelial cells: evidence for proteolysis of cell-surface molecules. J. Cell. Physiol. 168:625–637, 1996.

    Article  PubMed  CAS  Google Scholar 

  40. Ihrcke, N. S., L. E. Wrenshall, B. J. Lindman, and J. L. Platt. Role of heparan sulfate in immune system–blood vessel interactions. Immunol. Today 14:500–505, 1993.

    Article  PubMed  CAS  Google Scholar 

  41. Iigo, Y., M. Suematsu, T. Higashida, J. Oheda, K. Matsumoto, Y. Wakabayashi, Y. Ishimura, M. Miyasaka, and T. Takashi. Constitutive expression of ICAM-1 in rat microvascular systems analyzed by laser confocal microscopy. Am. J. Physiol. 273:H138–H147, 1997.

    PubMed  CAS  Google Scholar 

  42. Jung, U., K. E. Norman, K. Scharffetter-Kochanek, A. L. Beaudet, and K. Ley. Transit time of leukocytes rolling through venules controls cytokine-induced inflammatory cell recruitment in vivo. J. Clin. Invest. 102:1526–1533, 1998.

    Article  PubMed  CAS  Google Scholar 

  43. Kinashi, T., and K. Katagiri. Regulation of lymphocyte adhesion and migration by the small GTPase Rap1 and its effector molecule, RAPL. Immunol. Lett. 93:1–5, 2004.

    Article  PubMed  CAS  Google Scholar 

  44. Klitzman, B., and B. R. Duling. Microvascular hematocrit and red cell flow in resting and contracting striated muscle. Am. J. Physiol. 237:H481–H490, 1979.

    PubMed  CAS  Google Scholar 

  45. Laudanna, C., J. Y. Kim, G. Constantin, and E. Butcher. Rapid leukocyte integrin activation by chemokines. Immunol. Rev. 186:37–46, 2002.

    Article  PubMed  CAS  Google Scholar 

  46. Laurent, T. C., and J. R. Fraser. Hyaluronan. FASEB J. 6:2397–2404, 1992.

    PubMed  CAS  Google Scholar 

  47. Lawrence, M. B., L. V. McIntire, and S. G. Eskin. Effect of flow on polymorphonuclear leukocyte/endothelial cell adhesion. Blood 70:1284–1290, 1987.

    PubMed  CAS  Google Scholar 

  48. Lawrence, M. B., and T. A. Springer. Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins. Cell 65:859–873, 1991.

    Article  PubMed  CAS  Google Scholar 

  49. Lawrence, M. B., and T. A. Springer. Neutrophils roll on E-selectin. J. Immunol. 151:6338–6346, 1993.

    PubMed  CAS  Google Scholar 

  50. Ley, K., D. C. Bullard, M. L. Arbones, R. Bosse, D. Vestweber, T. F. Tedder, and A. L. Beaudet. Sequential contribution of L- and P-selectin to leukocyte rolling in vivo. J. Exp. Med. 181:669–675, 1995.

    Article  PubMed  CAS  Google Scholar 

  51. Li, Z., L. Li, H. R. Zielke, L. Cheng, R. Xiao, M. T. Crow, W. G. Stetler-Stevenson, J. Froehlich, and E. G. Lakatta. Increased expression of 72-kd type IV collagenase (MMP-2) in human aortic atherosclerotic lesions. Am. J. Pathol. 148:121–128, 1996.

    PubMed  CAS  Google Scholar 

  52. Li, Q., P. W. Park, C. L. Wilson, and W. C. Parks. Matrilysin shedding of syndecan-1 regulates chemokine mobilization and transepithelial efflux of neutrophils in acute lung injury. Cell 111:635–646, 2002.

    Article  PubMed  CAS  Google Scholar 

  53. Lipowsky, H. H., R. Sah, and A. Lescanic. Relative roles of doxycycline and cation chelation in endothelial glycan shedding and adhesion of leukocytes. Am. J. Physiol. Heart Circ. Physiol. 300:H415–H422, 2011.

    Article  PubMed  CAS  Google Scholar 

  54. Luft, J. H. Fine structures of capillary and endocapillary layer as revealed by ruthenium red. Fed. Proc. 25:1773–1783, 1966.

    PubMed  CAS  Google Scholar 

  55. Luo, B. H., C. V. Carman, and T. A. Springer. Structural basis of integrin regulation and signaling. Annu. Rev. Immunol. 25:619–647, 2007.

    Article  PubMed  CAS  Google Scholar 

  56. Mulivor, A. W., and H. H. Lipowsky. Role of glycocalyx in leukocyte–endothelial cell adhesion. Am. J. Physiol. Heart Circ. Physiol. 283:H1282–H1291, 2002.

    PubMed  CAS  Google Scholar 

  57. Mulivor, A. W., and H. H. Lipowsky. Inflammation- and ischemia-induced shedding of venular glycocalyx. Am. J. Physiol. Heart Circ. Physiol. 286:H1672–H1680, 2004.

    Article  PubMed  CAS  Google Scholar 

  58. Mulivor, A. W., and H. H. Lipowsky. Inhibition of glycan shedding and leukocyte–endothelial adhesion in postcapillary venules by suppression of matrixmetalloprotease activity with doxycycline. Microcirculation 16:657–666, 2009.

    Article  PubMed  CAS  Google Scholar 

  59. Park, P. W., O. Reizes, and M. Bernfield. Cell surface heparan sulfate proteoglycans: selective regulators of ligand–receptor encounters. J. Biol. Chem. 275:29923–29926, 2000.

    Article  PubMed  CAS  Google Scholar 

  60. Platt, J. L., A. P. Dalmasso, B. J. Lindman, N. S. Ihrcke, and F. H. Bach. The role of C5a and antibody in the release of heparan sulfate from endothelial cells. Eur. J. Immunol. 21:2887–2890, 1991.

    Article  PubMed  CAS  Google Scholar 

  61. Platt, J. L., G. M. Vercellotti, B. J. Lindman, T. R. Oegema, Jr., F. H. Bach, and A. P. Dalmasso. Release of heparan sulfate from endothelial cells. Implications for pathogenesis of hyperacute rejection. J. Exp. Med. 171:1363–1368, 1990.

    Article  PubMed  CAS  Google Scholar 

  62. Platts, S. H., and B. R. Duling. Adenosine A3 receptor activation modulates the capillary endothelial glycocalyx. Circ. Res. 94:77–82, 2004.

    Article  PubMed  CAS  Google Scholar 

  63. Platts, S. H., J. Linden, and B. R. Duling. Rapid modification of the glycocalyx caused by ischemia-reperfusion is inhibited by adenosine A2A receptor activation. Am. J. Physiol. Heart Circ. Physiol. 284:H2360–H2367, 2003.

    PubMed  CAS  Google Scholar 

  64. Poiseuille, J. L. M. Recherches sur les causes du mouvement du sang dans les vaisseaux capillaries. C. R. Acad. Sci. 6:554–560, 1835.

    Google Scholar 

  65. Potter, D. R., and E. R. Damiano. The hydrodynamically relevant endothelial cell glycocalyx observed in vivo is absent in vitro. Circ. Res. 102:770–776, 2008.

    Article  PubMed  CAS  Google Scholar 

  66. Pries, A. R., T. W. Secomb, and P. Gaehtgens. The endothelial surface layer. Pflugers Arch. 440:653–666, 2000.

    Article  PubMed  CAS  Google Scholar 

  67. Pries, A. R., T. W. Secomb, P. Gaehtgens, and J. F. Gross. Blood flow in microvascular networks. Experiments and simulation. Circ. Res. 67:826–834, 1990.

    PubMed  CAS  Google Scholar 

  68. Pries, A. R., T. W. Secomb, H. Jacobs, M. Sperandio, K. Osterloh, and P. Gaehtgens. Microvascular blood flow resistance: role of endothelial surface layer. Am. J. Physiol. 273:H2272–H2279, 1997.

    PubMed  CAS  Google Scholar 

  69. Purushothaman, A., T. Uyama, F. Kobayashi, S. Yamada, K. Sugahara, A. C. Rapraeger, and R. D. Sanderson. Heparanase-enhanced shedding of syndecan-1 by myeloma cells promotes endothelial invasion and angiogenesis. Blood 115:2449–2457, 2010.

    Article  PubMed  CAS  Google Scholar 

  70. Rapraeger, A. Transforming growth factor (type beta) promotes the addition of chondroitin sulfate chains to the cell surface proteoglycan (syndecan) of mouse mammary epithelia. J. Cell Biol. 109:2509–2518, 1989.

    Article  PubMed  CAS  Google Scholar 

  71. Rehm, M., D. Bruegger, F. Christ, P. Conzen, M. Thiel, M. Jacob, D. Chappell, M. Stoeckelhuber, U. Welsch, B. Reichart, K. Peter, and B. F. Becker. Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia. Circulation 116:1896–1906, 2007.

    Article  PubMed  CAS  Google Scholar 

  72. Reitsma, S., D. W. Slaaf, H. Vink, M. A. van Zandvoort, and M. G. oude Egbrink. The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch. 454:345–359, 2007.

    Article  PubMed  CAS  Google Scholar 

  73. Smith, M. L., D. S. Long, E. R. Damiano, and K. Ley. Near-wall micro-PIV reveals a hydrodynamically relevant endothelial surface layer in venules in vivo. Biophys. J. 85:637–645, 2003.

    Article  PubMed  CAS  Google Scholar 

  74. Spinale, F. G. Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. Physiol. Rev. 87:1285–1342, 2007.

    Article  PubMed  CAS  Google Scholar 

  75. Springer, T. A. Adhesion receptors of the immune system. Nature 346:425–434, 1990.

    Article  PubMed  CAS  Google Scholar 

  76. Squire, J. M., M. Chew, G. Nneji, C. Neal, J. Barry, and C. Michel. Quasi-periodic substructure in the microvessel endothelial glycocalyx: a possible explanation for molecular filtering? J. Struct. Biol. 136:239–255, 2001.

    Article  PubMed  CAS  Google Scholar 

  77. Subramanian, S. V., M. L. Fitzgerald, and M. Bernfield. Regulated shedding of syndecan-1 and -4 ectodomains by thrombin and growth factor receptor activation. J. Biol. Chem. 272:14713–14720, 1997.

    Article  PubMed  CAS  Google Scholar 

  78. Sutera, S. P., V. Seshadri, P. A. Croce, and R. M. Hochmuth. Capillary blood flow. II. Deformable model cells in tube flow. Microvasc. Res. 2:420–433, 1970.

    Article  PubMed  CAS  Google Scholar 

  79. Svennevig, K., T. Hoel, A. Thiara, S. Kolset, A. Castelheim, T. Mollnes, F. Brosstad, E. Fosse, and J. Svennevig. Syndecan-1 plasma levels during coronary artery bypass surgery with and without cardiopulmonary bypass. Perfusion 23:165–171, 2008.

    Article  PubMed  CAS  Google Scholar 

  80. Taraboletti, G., S. D’Ascenzo, P. Borsotti, R. Giavazzi, A. Pavan, and V. Dolo. Shedding of the matrix metalloproteinases MMP-2, MMP-9, and MT1-MMP as membrane vesicle-associated components by endothelial cells. Am. J. Pathol. 160:673–680, 2002.

    Article  PubMed  CAS  Google Scholar 

  81. Vink, H., and B. R. Duling. Identification of distinct luminal domains for macromolecules, erythrocytes, and leukocytes within mammalian capillaries. Circ. Res. 79:581–589, 1996.

    PubMed  CAS  Google Scholar 

  82. Vogl-Willis, C. A., and I. J. Edwards. High-glucose-induced structural changes in the heparan sulfate proteoglycan, perlecan, of cultured human aortic endothelial cells. Biochim. Biophys. Acta 1672:36–45, 2004.

    Article  PubMed  CAS  Google Scholar 

  83. Weinbaum, S., J. M. Tarbell, and E. R. Damiano. The structure and function of the endothelial glycocalyx layer. Annu. Rev. Biomed. Eng. 9:121–167, 2007.

    Article  PubMed  CAS  Google Scholar 

  84. Xu, J., D. Qu, N. L. Esmon, and C. T. Esmon. Metalloproteolytic release of endothelial cell protein C receptor. J. Biol. Chem. 275:6038–6044, 2000.

    Article  PubMed  CAS  Google Scholar 

  85. Yaras, N., M. Sariahmetoglu, A. Bilginoglu, A. Aydemir-Koksoy, A. Onay-Besikci, B. Turan, and R. Schulz. Protective action of doxycycline against diabetic cardiomyopathy in rats. Br. J. Pharmacol. 155:1174–1184, 2008.

    Article  PubMed  CAS  Google Scholar 

  86. Yu, W. H., and J. F. Woessner, Jr. Heparan sulfate proteoglycans as extracellular docking molecules for matrilysin (matrix metalloproteinase 7). J. Biol. Chem. 275:4183–4191, 2000.

    Article  PubMed  CAS  Google Scholar 

  87. Zarbock, A., and K. Ley. Neutrophil adhesion and activation under flow. Microcirculation 16:31–42, 2009.

    Article  PubMed  CAS  Google Scholar 

  88. Zcharia, E., J. Jia, X. Zhang, L. Baraz, U. Lindahl, T. Peretz, I. Vlodavsky, and J. P. Li. Newly generated heparanase knock-out mice unravel co-regulation of heparanase and matrix metalloproteinases. PLoS One 4:e5181, 2009.

    Article  PubMed  Google Scholar 

  89. Zuurbier, C. J., C. Demirci, A. Koeman, H. Vink, and C. Ince. Short-term hyperglycemia increases endothelial glycocalyx permeability and acutely decreases lineal density of capillaries with flowing red blood cells. J. Appl. Physiol. 99:1471–1476, 2005.

    Article  PubMed  Google Scholar 

  90. Zweifach, B. W. Structural makeup of capillary wall. Ann. N. Y. Acad. Sci. 61:670–677, 1955.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

This research was supported in part by NIH R01-HL39286-20.

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    Herbert H. Lipowsky

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Lipowsky, H.H. The Endothelial Glycocalyx as a Barrier to Leukocyte Adhesion and Its Mediation by Extracellular Proteases. Ann Biomed Eng 40, 840–848 (2012). https://doi.org/10.1007/s10439-011-0427-x

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