Targeting hyaluronan of the endothelial glycocalyx for therapeutic intervention

Current Opinion in Investigational Drugs

Volumn 11, Issue 9, 2010, Pages 997-1006

  Wheeler Jones, Caroline P D ^a   Farrar, Charlotte E ^a   Pitsillides, Andrew A ^a  

^a ROYAL VETERINARY COLLEGE   (United Kingdom)

Author keywords

Endothelial cell; endothelial dysfunction; extracellular matrix; glycocalyx; hyaluronan

Indexed keywords

ANGIOPOIETIN 1; ANTITHROMBIN; C REACTIVE PROTEIN; CYCLOOXYGENASE 2 INHIBITOR; ETANERCEPT; HYALURONIC ACID; HYALURONIDASE; HYDROCORTISONE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; ILOPROST; METFORMIN; NONSTEROID ANTIINFLAMMATORY AGENT; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR AGONIST; PROSTACYCLIN; PROSTAGLANDIN; REACTIVE OXYGEN METABOLITE; ROSUVASTATIN; TRICHOSTATIN A; URIDINE DIPHOSPHATE GLUCOSE DEHYDROGENASE; VASODILATOR AGENT;

ANTIINFLAMMATORY ACTIVITY; ARTERY THROMBOSIS; ATHEROSCLEROSIS; BIODEGRADATION; CARBOHYDRATE SYNTHESIS; CARDIOVASCULAR DISEASE; CELL HETEROGENEITY; CELL PROTECTION; CHEMICAL MODIFICATION; DRUG EFFECT; DRUG MECHANISM; DRUG TARGETING; ENDOTHELIAL DYSFUNCTION; ENDOTHELIAL GLYCOCALYX; ENDOTHELIUM CELL; EXTRACELLULAR MATRIX; HEART MUSCLE ISCHEMIA; HUMAN; HYPERCHOLESTEROLEMIA; MOLECULAR INTERACTION; MOLECULAR WEIGHT; NONHUMAN; OXIDATIVE STRESS; REVIEW; SIGNAL TRANSDUCTION; VASCULAR ENDOTHELIUM;

ANIMALS; ANTIGENS, CD44; ATHEROSCLEROSIS; ENDOTHELIAL CELLS; ENDOTHELIUM, VASCULAR; GLYCOCALYX; GLYCOSAMINOGLYCANS; HUMANS; HYALURONIC ACID; HYPERTENSION; INFLAMMATION; MOLECULAR TARGETED THERAPY;

EID: 77956235795     PISSN: 14724472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (100)

1. Stern R, Asari AA, Sugahara KN: Hyaluronan fragments: An information-rich system. Eur J Cell Biol (2006) 85(8):699-715.
2. Van Teeffelen JW, Brands J, Stroes ES, Vink H: Endothelial glycocalyx: Sweet shield of blood vessels. Trends Cardiovasc Med (2007) 17(3):101-105.
3. Reitsma S, Slaaf DW, Vink H, van Zandvoort MA, oude Egbrink MG: The endothelial glycocalyx: Composition, functions, and visualization. Pflugers Arch (2007) 454(3):345-359.
4. Perrin RM, Harper SJ, Bates DO: A role for the endothelial glycocalyx in regulating microvascular permeability in diabetes mellitus. Cell Biochem Biophys (2007) 49(2):65-72.
5. Montesano R, Mossaz A, Ryser JE, Orci L, Vassalli P: Leukocyte interleukins induce cultured endothelial cells to produce a highly organized, glycosaminoglycan-rich pericellular matrix. J Cell Biol (1984) 99(5):1706-1715.
6. Clarris BJ, Fraser JR: On the pericellular zone of some mammalian cells in vitro. Exp Cell Res (1968) 49(1):181-193.
7. Underhill CB, Toole BP: Transformation dependent loss of the hyaluronate-containing coats of cultured cells. J Cell Physiol (1982) 110(2):123-128.
8. Goldberg RL, Toole BP: Pericellular coat of chick embryo chondrocytes: Structural role of hyaluronate. J Cell Biol (1984) 99:2114-2122.
9. Knudson CB, Toole BP: Changes in the pericellular matrix during differentiation of limb bud mesoderm. Dev Biol (1985) 112(2):308-318.
10. McGuire PG, Castellot JJ Jr, Orkin RW: Size-dependent hyaluronate degradation by cultured cells. J Cell Physiol (1987) 133(2):267-276.
11. Knudson W, Knudson CB: Assembly of a chondrocyte-like pericellular matrix on non-chondrogenic cells. Role of the cell surface hyaluronan receptors in the assembly of a pericellular matrix. J Cell Sci (1991) 99(Pt 2):227-235.
12. Heldin P, Pertoft H: Synthesis and assembly of the hyaluronan-containing coats normal human mesothelial cells. Exp Cell Res (1993) 208(2):422-429.
13. Knudson W, Aguiar DJ, Hua Q, Knudson CB: CD44-anchored hyaluronan-rich pericellular matrices: An ultrastructural and biochemical analysis. Exp Cell Res (1996) 228(2):216-228.
14. Knudson CB: Hyaluronan receptor-directed assembly of chondrocyte pericellular matrix. J Cell Biol (1993) 120(3): 825-834.
15. Butler LM, Rainger GE, Nash GB: A role for the endothelial glycosaminoglycan hyaluronan in neutrophil recruitment by endothelial cells cultured for prolonged periods. Exp Cell Res (2009) 315(19):3433-3441.
16. Genasetti A, Vigetti D, Viola M, Karousou E, Moretto P, Rizzi M, Bartolini B, Clerici M, Pallotti F, De Luca G, Passi A: Hyaluronan and human endothelial cell behaviour. Connect Tissue Res (2008) 49(3):120-123.
17. DeAngelis PL, Papaconstantinou J, Weigel PH: Molecular cloning, identification and sequence of the hyaluronan synthase gene from group A Streptococcus pyogenes. J Biol Chem (1993) 268(26):19181-19184.
18. Dougherty BA, van de Rijn I: Molecular characterization of hasA from an operon required for hyaluronic acid synthesis in group A Streptococci. J Biol Chem (1994) 269(1):169-175.
19. Hascall VC, Majors AK, De La Motte CA, Evanko SP, Wang A, Drazba JA, Strong SA, Wight TN: Intracellular hyaluronan: A new frontier for inflammation? Biochim Biophys Acta (2004) 1673(1-2):3-12.
20. Schulz T, Schumacher U, Prehm P: Hyaluronan export by the ABC transporter MRP5 and its modulation by intracellular cGMP. J Biol Chem (2007) 282(29):20999-21004.
21. Recklies AD, White C, Melching L, Roughley PJ: Differential regulation and expression of hyaluronan synthases in human articular chondrocytes, synovial cells and osteosarcoma cells. Biochem J (2001) 354(Pt 1):17-24.
22. Goentzel BJ, Weigel PH, Steinberg RA: Recombinant human hyaluronan synthase 3 is phosphorylated in mammalian cells. Biochem J (2006) 396(2):347-354.
23. Itano N, Sawai T, Yoshida M, Lenas P, Yamada Y, Imagawa M, Shinomura T, Hamaguchi M, Yoshida Y, Ohnuki Y, Miyauchi S et al: Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties. J Biol Chem (1999) 274(35): 25085-25092.
24. Ginsburg V: Sugar nucleotides and the synthesis of carbohydrates. Adv Enzymol Relat Areas Mol Biol (1964) 26:35-88.
25. Molz RJ, Danishefsky I: Uridine diphosphate glucose dehydrogenase of rat tissue. Biochim Biophys Acta (1971) 250(1):6-13.
26. De Luca G, Speziale P, Rindi S, Balduini C, Castellani AA: Effect of some nucleotides on the regulation of glycosaminoglycan biosynthesis. Connect Tissue Res (1976) 4(4):247-254.
27. Vigetti D, Ori M, Viola M, Genasetti A, Karousou E, Rizzi M, Pallotti F, Nardi I, Hascall VC, De Luca G, Passi A: Molecular cloning and characterization of UDP-glucose dehydrogenase from the amphibian Xenopus laevis and its involvement in hyaluronan synthesis. J Biol Chem (2006) 281(12):8254-8263.
28. De Luca G, Castellani AA: Regulatory aspects of glycosaminoglycan biosynthesis. Acta Biol Hung (1984) 35 (2-4):109-121.
29. Beauchef G, Kypriotou M, Chadjichristos C, Widom RL, Porée B, Renard E, Moslemi S, Wegrowski Y, Maquart FX, Pujol JP, Galéra P: c-Krox down-regulates the expression of UDP-glucose dehydrogenase in chondrocytes. Biochem Biophys Res Commun (2005) 333(4):1123-1131.
30. Bontemps Y, Vuillermoz B, Antonicelli F, Perreau C, Danan JL, Maquart FX, Wegrowski Y: Specific protein-1 is a universal regulator of UDP-glucose dehydrogenase expression: Its positive involvement in transforming growth factor-â signaling and inhibition in hypoxia. J Biol Chem (2003) 278(24):21566-21575.
31. Bastow ER, Lamb KJ, Lewthwaite JC, Osborne AC, Kavanagh E, Wheeler-Jones CP, Pitsillides AA: Selective activation of the MEK-ERK pathway in forming joints is regulated by movement and promotes pericellular matrix formation. J Biol Chem (2005) 280(12):11749-11758.
32. Lewthwaite JC, Bastow ER, Lamb KJ, Blenis J, Wheeler-Jones CP, Pitsillides AA: A specific mechanomodulatory role for p38MAPK in embryonic joint articular surface cell MEK-ERK pathway regulation. J Biol Chem (2006) 281(16):11011-11018.
33. Pitsillides AA: Identifying and characterizing the joint cavity-forming cell. Cell Biochem Funct (2003) 21(3):235-240.
34. Bastow ER, Byers S, Golub SB, Clarkin CE, Pitsillides AA, Fosang AJ: Hyaluronan synthesis and degradation in cartilage and bone. Cell Mol Life Sci (2008) 65(3):395-413.
35. Slevin M, Krupinski J, Gaffney J, Matou S, West D, Delisser H, Savani RC, Kumar S: Hyaluronan-mediated angiogenesis in vascular disease: Uncovering RHAMM and CD44 receptor signalling pathways. Matrix Biol (2007) 26(1):58-68.
36. Mohamadzadeh M, DeGrendele H, Arizpe H, Estess P, Siegelman M: Proinflammatory stimuli regulate endothelial hyaluronan expression and CD44/HA-dependent primary adhesion. J Clin Invest (1998) 101(1):97-108.
37. Chappell D, Jacob M, Paul O, Rehm M, Welsch U, Stoeckelhuber M, Conzen P, Becker BF: The glycocalyx of the human umbilical vein endothelial cell. An impressive structure ex vivo but not in culture. Circ Res (2009) 104(11):1313-1317.
38. Potter DR, Jiang J, Damiano ER: The recovery time course of the endothelial cell glycocalyx in vivo and its implications in vitro. Circ Res (2009) 104(11):1318-1325.
39. Schiller J, Fuchs B, Arnhold J, Arnold K: Contribution of reactive oxygen species to cartilage degradation in rheumatic diseases: Molecular pathways, diagnosis and potential therapeutic strategies. Curr Med Chem (2003) 10(20):2123-2145.
40. Csoka AB, Frost GI, Stern R: The six hyaluronidase-like genes in the human and mouse genomes. Matrix Biol (2001) 20(8): 499-508.
41. Lepperdinger G, Strobl B, Kreil G: HYAL2, a human gene expressed in many cells, encodes a lysosomal hyaluronidase with a novel type of specificity. J Biol Chem (1998) 273(35): 22466-22470.
42. Weigel JA, Weigel PH: Characterization of the recombinant rat 175-kDa hyaluronan receptor for endocytosis (HARE). J Biol Chem (2003) 278(44):42802-42811.
43. Lesley J, Hyman R, Kincade PW: CD44 and its interaction with extracellular matrix. Adv Immunol (1993) 54:271-335.
44. Banerji S, Ni J, Wang SX, Clasper S, Su J, Tammi R, Jones M, Jackson DG: LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan. J Cell Biol (1999) 144(4):789-801.
45. Turley EA, Belch AJ, Poppema S, Pilarski LM: Expression and function of a receptor for hyaluronan mediated motility on normal and malignant B lymphocytes. Blood (1993) 81(12): 446-453.
46. Bono P, Rubin K, Higgins JM, Hynes RO: Layilin, a novel integral membrane protein, is a hyaluronan receptor. Mol Biol Cell (2001) 12(4):891-900.
47. van den Berg BM, Vink H, Spaan JA: The endothelial glycocalyx protects against myocardial edema. Circ Res (2003) 92(6): 592-594.
48. Pries AR, Kuebler WM: Normal endothelium. Handb Exp Pharmacol (2006) 176(Pt 1):1-40.
49. Nieuwdorp M, Meuwese MC, Mooij HL, Ince C, Broekhuizen LN, Kastelein JJ, Stroes ES, Vink H: Measuring endothelial glycocalyx dimensions in humans: A potential novel tool to monitor vascular vulnerability. J Appl Physiol (2008) 104(3):845-852.
50. Henry CB, Duling BR: Permeation of the luminal capillary glycocalyx is determined by hyaluronan. Am J Physiol Heart Circ Physiol (1999) 277(2 Pt 2):H508-H514.
51. Dowthwaite GP, Flannery CR, Flannelly J, Lewthwaite JC, Archer CW, Pitsillides AA: A mechanism underlying the movement requirement for synovial joint cavitation. Matrix Biol (2003) 22(4):311-322.
52. Bruegger D, Rehm M, Jacob M, Chappell D, Stoeckelhuber M, Welsch U, Conzen P, Becker BF: Exogenous nitric oxide requires an endothelial glycocalyx to prevent postischemic coronary vascular leak in guinea pig hearts. Critical Care (2008) 12(3):R73, doi:10.1186/cc6913.
53. Kmagai R, Lu X, Kassab GS: Role of glycocalyx in flow-induced production of nitric oxide and reactive oxygen species. Free Rad Biol Med (2009) 47(5):600-607.
54. Reitsma S, Slaaf DW, Vink H, van Zandvoort MA, oude Egbrink MG: The endothelial glycocalyx: Composition, functions and visualisation. Eur J Physiol (2007) 454(3):345-359.
55. Gouverneur M, Spaan JA, Pannekoek H, Fontijn RD, Vink H: Fluid shear stress stimulates incorporation of hyaluronan into endothelial cell glycocalyx. Am J Physiol Heart Circ Physiol (2006) 290(1):H458-H462.
56. Roemisch J, Gray E, Hoffmann JN, Wiedermann CJ: Antithrombin: A new look at the actions of a serine protease inhibitor. Blood Coagul Fibrinolysis (2002) 13(8):657-670.
57. Jeansson M, Haraldsson B: Morphological and functional evidence for an important role of the endothelial glycocalyx in the glomerular barrier. Am J Physiol Renal Physiol (2006) 290(1): F111-F116.
58. Matharu NM, Rainger GE, Vohra R, Nash GB: Effects of disturbed flow on endothelial cell function: Pathogenic implications of modified leukocyte recruitment. Biorheology (2006) 43(1):31-44.
59. Mulivor AW, Lipowsky HH: Role of glycocalyx in leukocyte-endothelial cell adhesion. Am J Physiol Heart Circ Physiol (2002) 283(4):H1282-H1291.
60. van den Berg BM, Spaan JA, Rolf TM, Vink H: Atherogenic region and diet diminish glycocalyx dimension and increase intima-to-media ratios at murine carotid artery bifurcation. Am J Physiol Heart Circ Physiol (2006) 290(2):H915-H920.
61. van den Berg BM, Spaan JA, Vink H: Impaired glycocalyx barrier properties contribute to enhanced intimal low-density lipoprotein accumulation at the carotid artery bifurcation in mice. Pflugers Arch (2009) 457(6):1199-1206.
62. Meuwese MC, Mooij HL, Nieuwdorp M, van Lith B, Marck R, Vink H, Kastelein JJ, Stroes ES: Partial recovery of the endothelial glycocalyx upon rosuvastatin therapy in patients with heterozygous familial hypercholesterolemia. J Lipid Res (2009) 50(1):148-153.
63. Nieuwdorp M, van Haeften TW, Gouverneur MC, Mooij HL, van Lieshout MH, Levi M, Meijers JC, Holleman F, Hoekstra JB, Vink H, Kastelein JJ et al: Loss of endothelial glycocalyx during acute hyperglycemia coincides with endothelial dysfunction and coagulation activation in vivo. Diabetes (2006) 55(2):480-486.
64. Devaraj S, Yun JM, Adamson G, Galvez J, Jialal I: C-reactive protein impairs the endothelial glycocalyx resulting in endothelial dysfunction. Cardiovasc Res (2009) 84(3):479-484.
65. Gouverneur M, Berg B, Nieuwdorp M, Stroes E, Vink H: Vasculoprotective properties of the endothelial glycocalyx: Effects of fluid shear stress. J Intern Med (2006) 259(4): 393-400.
66. Platts SH, Linden J, Duling BR: Rapid modification of the glycocalyx caused by ischemia-reperfusion is inhibited by adenosine A2A receptor activation. Am J Physiol Heart Circ Physiol (2003) 284(6):H2360-H2367
67. Henry CB, Duling BR: TNF-á increases entry of macromolecules into luminal endothelial cell glycocalyx. Am J Physiol Heart Circ Physiol (2000) 279(6):H2815-H2823.
68. Rubio-Gayosso I, Platts SH, Duling BR: Reactive oxygen species mediate modification of glycocalyx during ischemia- reperfusion injury. Am J Physiol Heart Circ Physiol (2006) 290(6):H2247-H2256.
69. Riessen R, Wight TN, Pastore C, Henley C, Isner JM: Distribution of hyaluronan during extracellular matrix remodeling in human restenotic arteries and balloon-injured rat carotid arteries. Circulation (1996) 93(6):1141-1147.
70. Kucur M, Karadag B, Isman FK, Ataev Y, Duman D, Karadag N, Ongen Z, Vural VA: Plasma hyaluronidase activity as an indicator of atherosclerosis in patients with coronary artery disease. Bratisl Lek Listy (2009) 110(1):21-26.
71. van den Boom M, Sarbia M, von Wnuck Lipinski K, Mann P, Meyer-Kirchrath J, Rauch BH, Grabitz K, Levkau B, Schrör K, Fischer JW: Differential regulation of hyaluronic acid synthase isoforms in human saphenous vein smooth muscle cells: Possible implications for vein graft stenosis. Circ Res (2006) 98(1):36-44.
72. Marzoll A, Nagy N, Wördehoff L, Dai G, Fries S, Lindner V, Grosser T, Fischer JW: Cyclooxygenase inhibitors repress vascular hyaluronan synthesis in murine atherosclerosis and neointimal thickening. J Cell Mol Med (2009) 13(9B):3713-3719.
73. Wilkinson TS, Bressler SL, Evanko SP, Braun KR, Wight TN: Overexpression of hyaluronan synthases alters vascular smooth muscle cell phenotype and promotes monocyte adhesion. J Cell Physiol (2006) 206(2):378-385.
74. Chai S, Chai Q, Danielsen CC, Hjorth P, Nyengaard JR, Ledet T, Yamaguchi Y, Rasmussen LM, Wogensen L: Overexpression of hyaluronan in the tunica media promotes the development of atherosclerosis. Circ Res (2005) 96(5):583-591.
75. Lauer ME, Mukhopadhyay D, Fulop C, de la Motte CA, Majors AK, Hascall VC: Primary murine airway smooth muscle cells exposed to poly(I,C) or tunicamycin synthesize a leukocyte-adhesive hyaluronan matrix. J Biol Chem (2009) 284(8): 5299-5312.
76. Nieuwdorp M, Meuwese MC, Mooij HL, van Lieshout MH, Hayden A, Levi M, Meijers JC, Ince C, Kastelein JJ, Vink H, Stroes ES: Tumour necrosis factor-á inhibition protects against endotoxin-induced endothelial glycocalyx perturbation. Atherosclerosis (2009) 202(1):296-303.
77. Agren UM, Tammi RH, Tammi MI: Reactive oxygen species contribute to epidermal hyaluronan catabolism in human skin organ culture. Free Rad Biol Med (1997) 23(7):996-1001.
78. Moseley R, Waddington RJ, Embery G: Degradation of glycosaminoglycans by reactive oxygen species derived from stimulated polymorphonuclear leukocytes. Biochim Biophys Acta (1997) 1362(2-3):221-231.
79. Constantinescu AA, Vink H, Spaan JA: Elevated capillary tube hematocrit reflects degradation of endothelial cell glycocalyx by oxidised LDL. Am J Physiol Heart Circ Physiol (2001) 280(3):H1051-H1057.
80. Rehm M, Bruegger D, Christ F, Conzen P, Thiel M, Jacob M, Chappell D, Stoeckelhuber M, Welsch U, Reichart B, Peter K et al: Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia. Circulation (2007) 116(17):1896-1906.
81. Marechal X, Favory R, Joulin O, Montaigne D, Hassoun S, Decoster B, Zerimech F, Neviere R: Endothelial glycocalyx damage during endotoxemia coincides with microcirculatory dysfunction and vascular oxidative stress. Shock (2008) 29(5):572-576.
82. Chappell D, Jacob M, Hofmann-Kiefer K, Rehm M, Welsch U, Conzen P, Becker BF: Antithrombin reduces shedding of the endothelial glycocalyx following ischaemia/reperfusion. Cardiovasc Res (2009) 83(2):388-396.
83. Chappell D, Jacob M, Hofmann-Kiefer K, Bruegger D, Rehm M, Conzen P, Welsch U, Becker BF: Hydrocortisone preserves vascular barrier by protecting the endothelial cell glycocalyx. Anesthesiology (2007) 107(5):776-784.
84. Chappell D, Hofmann-Kiefer K, Jacob M, Rehm M, Briegel J, Welsch U, Conzen P, Becker BF: TNF-á induced shedding of the endothelial glycocalyx is prevented by hydrocortisone and antithrombin. Basic Res Cardiol (2009) 104(1):78-89.
85. Wheeler-Jones CP: Regulation of endothelial prostacyclin synthesis by protease-activated receptors: Mechanisms and significance. Pharmacol Rep (2008) 60(1):109-118.
86. Houliston RA, Keogh RJ, Sugden D, Dudhia J, Carter TD, Wheeler-Jones CP: Protease-activated receptors upregulate cyclooxygenase-2 expression in human endothelial cells. Thromb Haemost (2002) 88(2):321-328.
87. Syeda F, Grosjean J, Houliston RA, Keogh RJ, Carter TD, Paleolog E, Wheeler-Jones CP: Cyclooxygenase-2 induction and prostacyclin release by protease-activated receptors in endothelial cells requires co-operation between mitogen-activated protein kinase and NF-êB pathways. J Biol Chem (2006) 281(17):11792-11804.
88. Warner TD, Mitchell JA: COX-2 selectivity alone does not define the cardiovascular risks associated with non-steroidal anti-inflammatory drugs. Lancet (2006) 371(9608):270-273.
89. VanTeeffelen JW, Constantinescu AA, Brands J, Spaan JA, Vink H: Bradykinin- and sodium nitroprusside-induced increases in capillary tube haematocrit in mouse cremaster muscle are associated with impaired glycocalyx barrier properties. J Physiol (2008) 586(13):3207-3218.
90. Salmon AH, Neal CR, Sage LM, Glass CA, Harper SJ, Bates DO: Angiopoietin-1 alters microvascular permeability coefficients in vivo via modification of endothelial glycocalyx. Cardiovasc Res (2009) 83(1):24-33.
91. Bruegger D, Jacob M, Rehm M, Loetsch M, Welsch U, Conzen P, Becker BF: Atrial natriuretic peptide induces shedding of endothelial glycocalyx in coronary vascular bed of guinea-pig hearts. Am J Physiol Heart Circ Physiol (2005) 289(5):H1993-H1999.
92. Inoue K, Kobayashi M, Yano K, Miura M, Izumi A, Mataki C, Doi T, Hamakubo T, Reid PC, Hume DA, Yoshida M et al: Histone deacetylase inhibitor reduces monocyte adhesion to endothelium through the suppression of vascular cell adhesion molecule-1 expression. Arterioscler Thromb Vasc Biol (2006) 26(12):2652-2659.
93. Granger A, Abdullah I, Huebner F, Stout A, Wang T, Huebner T, Epstein JA, Gruber PJ: Histone deacetylase inhibition reduces myocardial ischemia-reperfusion injury in mice. FASEB J (2008) 22(10):3549-3560.
94. Huang NL, Chiang SH, Hsueh CH, Liang YJ, Chen YJ, Lai LP: Metformin inhibits TNF-á-induced IêB kinase phosphorylation, IêB-á degradation and IL-6 production in endothelial cells through PI3K-dependent AMPK phosphorylation. Int J Cardiol (2009) 134(2):169-175.
95. Matsumoto T, Noguchi E, Ishida K, Kobayashi T, Yamada N, Kamata K: Metformin normalizes endothelial function by suppressing vasoconstrictor prostanoids in mesenteric arteries from OLETF rats, a model of type 2 diabetes. Am J Physiol Heart Circ Physiol (2008) 295(3):H1165-H1176.
96. Rehm M, Zahler S, Lötsch M, Welsch U, Conzen P, Jacob M, Becker BF: Endothelial glycocalyx as an additional barrier determining extravasation of 6% hydroxyethyl starch or 5% albumin solutions in the coronary vascular bed. Anesthesiology (2004) 100(5):1211-1223.
97. Mulivor AW, Lipowsky HH: Inflammation- and ischemia-induced shedding of venular glycocalyx. Am J Physiol Heart Circ Physiol (2004) 286(5):H1672-H1680.
98. Kultti A, Pasonen-Seppänen S, Jauhiainen M, Rilla KJ, Kärnä R, Pyöriä E, Tammi RH, Tammi MI: 4-Methylumbelliferone inhibits hyaluronan synthesis by depletion of cellular UDP-glucuronic acid and downregulation of hyaluronan synthase 2 and 3. Exp Cell Res (2009) 315(11):1914-1923.
99. Adamia S, Maxwell CA, Pilarski LM: Hyaluronan and hyaluronan synthases: Potential therapeutic targets in cancer. Curr Drug Targets Cardiovasc Haematol Disord (2005) 5(1):3-14.
100. Rehm M, Haller M, Orth V, Kreimeier U, Jacob M, Dressel H, Mayer S, Brechtelsbauer H, Finsterer U: Changes in blood volume and hematocrit during acute preoperative volume loading with 5% albumin or 6% hetastarch solutions in patients before radical hysterectomy. Anesthesiology (2001) 95(4): 849-856.