Role of the endothelium in inflammatory bowel diseases

World Journal of Gastroenterology

Volumn 17, Issue 5, 2011, Pages 578-593

  Cromer, Walter E ^a   Mathis, J Michael ^a   Granger, Daniel N ^a   Chaitanya, Ganta V ^a   Alexander, J Steven ^a  

^a LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER   (United States)

Author keywords

Adhesion molecules; Chemokines; Crohn's disease; Cytokines; Endothelium; Growth factors; Inflammation; Microvasculature; Nitric oxide; Ulcerative colitis

Indexed keywords

ANGIOSTATIN; BEVACIZUMAB; CYCLOSPORIN A; ENDOTHELIAL NITRIC OXIDE SYNTHASE; FRACTALKINE; INTERLEUKIN 1; INTERLEUKIN 10; MITOGEN ACTIVATED PROTEIN KINASE P38; NATALIZUMAB; PHOSPHOLIPASE C; THALIDOMIDE; TOLL LIKE RECEPTOR; TUMOR NECROSIS FACTOR ALPHA; VASCULOTROPIN A; VASCULOTROPIN RECEPTOR 1;

ANGIOGENESIS; ARTICLE; CELL EXPANSION; COLORECTAL CANCER; CROHN DISEASE; ENDOTHELIAL PROGENITOR CELL; ENDOTHELIUM; ENDOTHELIUM CELL; ENTERITIS; ENZYME ACTIVITY; HUMAN; LEUKOCYTE AGGREGATION; NONHUMAN; PATHOLOGY; PROTEIN INTERACTION; SIGNAL TRANSDUCTION; ULCERATIVE COLITIS; UMBILICAL VEIN ENDOTHELIAL CELL;

EID: 79955931063     PISSN: 10079327     EISSN: None     Source Type: Journal    
DOI: 10.3748/wjg.v17.i5.578     Document Type: Article

References (244)

1. Sands BE, Kaplan GG. The role of TNF alpha in ulcerative colitis. J Clin Pharmacol 2007; 47: 930-941
2. Parkes M, Satsangi J, Jewell D. Contribution of the IL-2 and IL-10 genes to inflammatory bowel disease (IBD) susceptibility. Clin Exp Immunol 1998; 113: 28-32
3. Boyko EJ, Perera DR, Koepsell TD, Keane EM, Inui TS. Coffee and alcohol use and the risk of ulcerative colitis. Am J Gastroenterol 1989; 84: 530-534
4. Langhorst J, Cobelens PM, Kavelaars A, Heijnen CJ, Benson S, Rifaie N, Dobos GJ, Schedlowski M, Elsenbruch S. Stressrelated peripheral neuroendocrine-immune interactions in women with ulcerative colitis. Psychoneuroendocrinology 2007; 32: 1086-1096
5. Langhorst J, Wieder A, Michalsen A, Musial F, Dobos GJ, Rueffer A. Activated innate immune system in irritable bowel syndrome? Gut 2007; 56: 1325-1326
6. Pousa ID, Gisbert JP. Gastric angiogenesis and Helicobacter pylori infection. Rev Esp Enferm Dig 2006; 98: 527-541
7. Hibi T, Ogata H. Novel pathophysiological concepts of inflammatory bowel disease. J Gastroenterol 2006; 41: 10-16
8. Garrett WS, Lord GM, Punit S, Lugo-Villarino G, Mazmanian SK, Ito S, Glickman JN, Glimcher LH. Communicable ulcerative colitis induced by T-bet deficiency in the innate immune system. Cell 2007; 131: 33-45
9. Sands BE. Inflammatory bowel disease: past, present, and future. J Gastroenterol 2007; 42: 16-25
10. Mayer L. Evolving paradigms in the pathogenesis of IBD. J Gastroenterol 2010; 45: 9-16
11. Ruyssers NE, De Winter BY, De Man JG, Loukas A, Herman AG, Pelckmans PA, Moreels TG. Worms and the treatment of inflammatory bowel disease: are molecules the answer? Clin Dev Immunol 2008; 2008: 567314
12. Fiasse R, Latinne D. Intestinal helminths: a clue explaining the low incidence of inflammatory bowel diseases in Subsaharan Africa? Potential benefits and hazards of helminth therapy. Acta Gastroenterol Belg 2006; 69: 418-422
13. Moreels TG, Pelckmans PA. Gastrointestinal parasites: potential therapy for refractory inflammatory bowel diseases. Inflamm Bowel Dis 2005; 11: 178-184
14. Sandborn WJ, Targan SR. Biologic therapy of inflammatory bowel disease. Gastroenterology 2002; 122: 1592-1608
15. Sawa Y, Oshitani N, Adachi K, Higuchi K, Matsumoto T, Arakawa T. Comprehensive analysis of intestinal cytokine messenger RNA profile by real-time quantitative polymerase chain reaction in patients with inflammatory bowel disease. Int J Mol Med 2003; 11: 175-179
16. Latinne D, Fiasse R. New insights into the cellular immunology of the intestine in relation to the pathophysiology of inflammatory bowel diseases. Acta Gastroenterol Belg 2006; 69: 393-405
17. Chidlow JH Jr, Shukla D, Grisham MB, Kevil CG. Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues. Am J Physiol Gastrointest Liver Physiol 2007; 293: G5-G18
18. Jiang HQ, Thurnheer MC, Zuercher AW, Boiko NV, Bos NA, Cebra JJ. Interactions of commensal gut microbes with subsets of B- and T-cells in the murine host. Vaccine 2004; 22: 805-811
19. Oshima T, Laroux FS, Coe LL, Morise Z, Kawachi S, Bauer P, Grisham MB, Specian RD, Carter P, Jennings S, Granger DN, Joh T, Alexander JS. Interferon-gamma and interleukin- 10 reciprocally regulate endothelial junction integrity and barrier function. Microvasc Res 2001; 61: 130-143
20. Dharmani P, Chadee K. Biologic therapies against inflammatory bowel disease: a dysregulated immune system and the cross talk with gastrointestinal mucosa hold the key. Curr Mol Pharmacol 2008; 1: 195-212
21. Yacyshyn BR. Adhesion molecule therapeutics in IBD. Inflamm Bowel Dis 2008; 14 Suppl 2: S279-S280
22. Danese S, Dejana E, Fiocchi C. Immune regulation by microvascular endothelial cells: directing innate and adaptive immunity, coagulation, and inflammation. J Immunol 2007; 178: 6017-6022
23. Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, Pober JS, Wick TM, Konkle BA, Schwartz BS, Barnathan ES, McCrae KR, Hug BA, Schmidt AM, Stern DM. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 1998; 91: 3527-3561
24. Haraldsen G, Rugtveit J, Kvale D, Scholz T, Muller WA, Hovig T, Brandtzaeg P. Isolation and longterm culture of human intestinal microvascular endothelial cells. Gut 1995; 37: 225-234
25. Haraldsen G, Kvale D, Lien B, Farstad IN, Brandtzaeg P. Cytokine-regulated expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in human microvascular endothelial cells. J Immunol 1996; 156: 2558-2565
26. Nilsen EM, Johansen FE, Jahnsen FL, Lundin KE, Scholz T, Brandtzaeg P, Haraldsen G. Cytokine profiles of cultured microvascular endothelial cells from the human intestine. Gut 1998; 42: 635-642
27. Binion DG, Rafiee P, Ramanujam KS, Fu S, Fisher PJ, Rivera MT, Johnson CP, Otterson MF, Telford GL, Wilson KT. Deficient iNOS in inflammatory bowel disease intestinal microvascular endothelial cells results in increased leukocyte adhesion. Free Radic Biol Med 2000; 29: 881-888
28. Binion DG, West GA, Volk EE, Drazba JA, Ziats NP, Petras RE, Fiocchi C. Acquired increase in leucocyte binding by intestinal microvascular endothelium in inflammatory bowel disease. Lancet 1998; 352: 1742-1746
29. Sessa WC. Molecular control of blood flow and angiogenesis: role of nitric oxide. J Thromb Haemost 2009; 7 Suppl 1: 35-37
30. Binion DG, Fu S, Ramanujam KS, Chai YC, Dweik RA, Drazba JA, Wade JG, Ziats NP, Erzurum SC, Wilson KT. INOS expression in human intestinal microvascular endothelial cells inhibits leukocyte adhesion. Am J Physiol 1998; 275: G592-G603
31. Petersson J, Schreiber O, Steege A, Patzak A, Hellsten A, Phillipson M, Holm L. eNOS involved in colitis-induced mucosal blood flow increase. Am J Physiol Gastrointest Liver Physiol 2007; 293: G1281-G1287
32. Spyridopoulos I, Luedemann C, Chen D, Kearney M, Chen D, Murohara T, Principe N, Isner JM, Losordo DW. Divergence of angiogenic and vascular permeability signaling by VEGF: inhibition of protein kinase C suppresses VEGFinduced angiogenesis, but promotes VEGF-induced, NOdependent vascular permeability. Arterioscler Thromb Vasc Biol 2002; 22: 901-906
33. Breslin JW, Pappas PJ, Cerveira JJ, Hobson RW 2nd, Durán WN. VEGF increases endothelial permeability by separate signaling pathways involving ERK-1/2 and nitric oxide. Am J Physiol Heart Circ Physiol 2003; 284: H92-H100
34. Rousseau S, Houle F, Kotanides H, Witte L, Waltenberger J, Landry J, Huot J. Vascular endothelial growth factor (VEGF)-driven actin-based motility is mediated by VEGFR2 and requires concerted activation of stress-activated protein kinase 2 (SAPK2/p38) and geldanamycin-sensitive phosphorylation of focal adhesion kinase. J Biol Chem 2000; 275: 10661-10672
35. Mihaescu A, Santen S, Jeppsson B, Thorlacius H. p38 Mitogen- activated protein kinase signalling regulates vascular inflammation and epithelial barrier dysfunction in an experimental model of radiation-induced colitis. Br J Surg 2010; 97: 226-234
36. Kumar P, Shen Q, Pivetti CD, Lee ES, Wu MH, Yuan SY. Molecular mechanisms of endothelial hyperpermeability: implications in inflammation. Expert Rev Mol Med 2009; 11: e19
37. Vetrano S, Danese S. The role of JAM-A in inflammatory bowel disease: unrevealing the ties that bind. Ann N Y Acad Sci 2009; 1165: 308-313
38. Horowitz S, Binion DG, Nelson VM, Kanaa Y, Javadi P, Lazarova Z, Andrekopoulos C, Kalyanaraman B, Otterson MF, Rafiee P. Increased arginase activity and endothelial dysfunction in human inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol 2007; 292: G1323-G1336
39. Förstermann U. Janus-faced role of endothelial NO synthase in vascular disease: uncoupling of oxygen reduction from NO synthesis and its pharmacological reversal. Biol Chem 2006; 387: 1521-1533
40. Förstermann U, Münzel T. Endothelial nitric oxide synthase in vascular disease: from marvel to menace. Circulation 2006; 113: 1708-1714
41. Hatoum OA, Binion DG, Otterson MF, Gutterman DD. Acquired microvascular dysfunction in inflammatory bowel disease: Loss of nitric oxide-mediated vasodilation. Gastroenterology 2003; 125: 58-69
42. Palatka K, Serfozo Z, Veréb Z, Hargitay Z, Lontay B, Erdodi F, Bánfalvi G, Nemes Z, Udvardy M, Altorjay I. Changes in the expression and distribution of the inducible and endothelial nitric oxide synthase in mucosal biopsy specimens of inflammatory bowel disease. Scand J Gastroenterol 2005; 40: 670-680
43. Sasaki M, Bharwani S, Jordan P, Elrod JW, Grisham MB, Jackson TH, Lefer DJ, Alexander JS. Increased disease activity in eNOS-deficient mice in experimental colitis. Free Radic Biol Med 2003; 35: 1679-1687
44. Oshima T, Jordan P, Grisham MB, Alexander JS, Jennings M, Sasaki M, Manas K. TNF-alpha induced endothelial MAd- CAM-1 expression is regulated by exogenous, not endogenous nitric oxide. BMC Gastroenterol 2001; 1: 5
45. Kevil CG, Ohno N, Gute DC, Okayama N, Robinson SA, Chaney E, Alexander JS. Role of cadherin internalization in hydrogen peroxide-mediated endothelial permeability. Free Radic Biol Med 1998; 24: 1015-1022
46. Kevil CG, Oshima T, Alexander B, Coe LL, Alexander JS. H(2)O(2)-mediated permeability: role of MAPK and occludin. Am J Physiol Cell Physiol 2000; 279: C21-C30
47. Kevil CG, Okayama N, Alexander JS. H(2)O(2)-mediated permeability II: importance of tyrosine phosphatase and kinase activity. Am J Physiol Cell Physiol 2001; 281: C1940-C1947
48. Palatka K, Serfozo Z, Veréb Z, Bátori R, Lontay B, Hargitay Z, Nemes Z, Udvardy M, Erdodi F, Altorjay I. Effect of IBD sera on expression of inducible and endothelial nitric oxide synthase in human umbilical vein endothelial cells. World J Gastroenterol 2006; 12: 1730-1738
49. Krieglstein CF, Anthoni C, Cerwinka WH, Stokes KY, Russell J, Grisham MB, Granger DN. Role of blood- and tissueassociated inducible nitric-oxide synthase in colonic inflammation. Am J Pathol 2007; 170: 490-496
50. Aoi Y, Terashima S, Ogura M, Nishio H, Kato S, Takeuchi K. Roles of nitric oxide (NO) and NO synthases in healing of dextran sulfate sodium-induced rat colitis. J Physiol Pharmacol 2008; 59: 315-336
51. Elrod JW, Laroux FS, Houghton J, Carpenter A, Ando T, Jennings MH, Grisham M, Walker N, Alexander JS. DSSinduced colitis is exacerbated in STAT-6 knockout mice. Inflamm Bowel Dis 2005; 11: 883-889
52. Van Crombruggen K, Van Nassauw L, Demetter P, Cuvelier C, Timmermans JP, Lefebvre RA. Influence of soluble guanylate cyclase inhibition on inflammation and motility disturbances in DSS-induced colitis. Eur J Pharmacol 2008; 579: 337-349
53. Conner EM, Brand S, Davis JM, Laroux FS, Palombella VJ, Fuseler JW, Kang DY, Wolf RE, Grisham MB. Proteasome inhibition attenuates nitric oxide synthase expression, VCAM-1 transcription and the development of chronic colitis. J Pharmacol Exp Ther 1997; 282: 1615-1622
54. Grisham MB, Palombella VJ, Elliott PJ, Conner EM, Brand S, Wong HL, Pien C, Mazzola LM, Destree A, Parent L, Adams J. Inhibition of NF-kappa B activation in vitro and in vivo: role of 26S proteasome. Methods Enzymol 1999; 300: 345-363
55. Deban L, Correale C, Vetrano S, Malesci A, Danese S. Multiple pathogenic roles of microvasculature in inflammatory bowel disease: a Jack of all trades. Am J Pathol 2008; 172: 1457-1466
56. Ogawa H, Rafiee P, Heidemann J, Fisher PJ, Johnson NA, Otterson MF, Kalyanaraman B, Pritchard KA Jr, Binion DG. Mechanisms of endotoxin tolerance in human intestinal microvascular endothelial cells. J Immunol 2003; 170: 5956-5964
57. Gewirtz AT. Flag in the crossroads: flagellin modulates innate and adaptive immunity. Curr Opin Gastroenterol 2006; 22: 8-12
58. Hokari R, Miura S. Neutrophil elastase in colitis: more than a marker of disease activity? J Gastroenterol 2006; 41: 395-396
59. Morohoshi Y, Matsuoka K, Chinen H, Kamada N, Sato T, Hisamatsu T, Okamoto S, Inoue N, Takaishi H, Ogata H, Iwao Y, Hibi T. Inhibition of neutrophil elastase prevents the development of murine dextran sulfate sodium-induced colitis. J Gastroenterol 2006; 41: 318-324
60. Maaser C, Heidemann J, von Eiff C, Lugering A, Spahn TW, Binion DG, Domschke W, Lugering N, Kucharzik T. Human intestinal microvascular endothelial cells express Toll-like receptor 5: a binding partner for bacterial flagellin. J Immunol 2004; 172: 5056-5062
61. Vijay-Kumar M, Aitken JD, Gewirtz AT. Toll like receptor- 5: protecting the gut from enteric microbes. Semin Immunopathol 2008; 30: 11-21
62. Vijay-Kumar M, Sanders CJ, Taylor RT, Kumar A, Aitken JD, Sitaraman SV, Neish AS, Uematsu S, Akira S, Williams IR, Gewirtz AT. Deletion of TLR5 results in spontaneous colitis in mice. J Clin Invest 2007; 117: 3909-3921
63. Vijay-Kumar M, Wu H, Aitken J, Kolachala VL, Neish AS, Sitaraman SV, Gewirtz AT. Activation of toll-like receptor 3 protects against DSS-induced acute colitis. Inflamm Bowel Dis 2007; 13: 856-864
64. Heidemann J, Rüther C, Kebschull M, Domschke W, Brüwer M, Koch S, Kucharzik T, Maaser C. Expression of IL-12-related molecules in human intestinal microvascular endothelial cells is regulated by TLR3. Am J Physiol Gastrointest Liver Physiol 2007; 293: G1315-G1324
65. Kawachi S, Morise Z, Jennings SR, Conner E, Cockrell A, Laroux FS, Chervenak RP, Wolcott M, van der Heyde H, Gray L, Feng L, Granger DN, Specian RA, Grisham MB. Cytokine and adhesion molecule expression in SCID mice reconstituted with CD4+ T cells. Inflamm Bowel Dis 2000; 6: 171-180
66. Kawachi S, Jennings S, Panes J, Cockrell A, Laroux FS, Gray L, Perry M, van der Heyde H, Balish E, Granger DN, Specian RA, Grisham MB. Cytokine and endothelial cell adhesion molecule expression in interleukin-10-deficient mice. Am J Physiol Gastrointest Liver Physiol 2000; 278: G734-G743
67. Polzer K, Baeten D, Soleiman A, Distler J, Gerlag DM, Tak PP, Schett G, Zwerina J. Tumour necrosis factor blockade increases lymphangiogenesis in murine and human arthritic joints. Ann Rheum Dis 2008; 67: 1610-1616
68. Heidenreich R, Röcken M, Ghoreschi K. Angiogenesis drives psoriasis pathogenesis. Int J Exp Pathol 2009; 90: 232-248
69. Hatoum OA, Heidemann J, Binion DG. The intestinal microvasculature as a therapeutic target in inflammatory bowel disease. Ann N Y Acad Sci 2006; 1072: 78-97
70. Pufe T, Lemke A, Kurz B, Petersen W, Tillmann B, Grodzinsky AJ, Mentlein R. Mechanical overload induces VEGF in cartilage discs via hypoxia-inducible factor. Am J Pathol 2004; 164: 185-192
71. Danese S, Sans M, Scaldaferri F, Sgambato A, Rutella S, Cittadini A, Piqué JM, Panes J, Katz JA, Gasbarrini A, Fiocchi C. TNF-alpha blockade down-regulates the CD40/CD40L pathway in the mucosal microcirculation: a novel anti-inflammatory mechanism of infliximab in Crohn's disease. J Immunol 2006; 176: 2617-2624
72. Romer LH, McLean NV, Yan HC, Daise M, Sun J, DeLisser HM. IFN-gamma and TNF-alpha induce redistribution of PECAM-1 (CD31) on human endothelial cells. J Immunol 1995; 154: 6582-6592
73. Kosmadaki MG, Yaar M, Arble BL, Gilchrest BA. UV induces VEGF through a TNF-alpha independent pathway. FASEB J 2003; 17: 446-448
74. Scheinin T, Butler DM, Salway F, Scallon B, Feldmann M. Validation of the interleukin-10 knockout mouse model of colitis: antitumour necrosis factor-antibodies suppress the progression of colitis. Clin Exp Immunol 2003; 133: 38-43
75. Lindsay JO, Ciesielski CJ, Scheinin T, Brennan FM, Hodgson HJ. Local delivery of adenoviral vectors encoding murine interleukin 10 induces colonic interleukin 10 production and is therapeutic for murine colitis. Gut 2003; 52: 981-987
76. Lindsay J, Van Montfrans C, Brennan F, Van Deventer S, Drillenburg P, Hodgson H, Te Velde A, Sol Rodriguez Pena M. IL-10 gene therapy prevents TNBS-induced colitis. Gene Ther 2002; 9: 1715-1721
77. Papadakis KA. Chemokines in inflammatory bowel disease. Curr Allergy Asthma Rep 2004; 4: 83-89
78. Barcelos LS, Coelho AM, Russo RC, Guabiraba R, Souza AL, Bruno-Lima G Jr, Proudfoot AE, Andrade SP, Teixeira MM. Role of the chemokines CCL3/MIP-1 alpha and CCL5/RANTES in sponge-induced inflammatory angiogenesis in mice. Microvasc Res 2009; 78: 148-154
79. Wu Y, Li YY, Matsushima K, Baba T, Mukaida N. CCL3- CCR5 axis regulates intratumoral accumulation of leukocytes and fibroblasts and promotes angiogenesis in murine lung metastasis process. J Immunol 2008; 181: 6384-6393
80. Eyman D, Damodarasamy M, Plymate SR, Reed MJ. CCL5 secreted by senescent aged fibroblasts induces proliferation of prostate epithelial cells and expression of genes that modulate angiogenesis. J Cell Physiol 2009; 220: 376-381
81. Rivera-Nieves J, Ho J, Bamias G, Ivashkina N, Ley K, Oppermann M, Cominelli F. Antibody blockade of CCL25/ CCR9 ameliorates early but not late chronic murine ileitis. Gastroenterology 2006; 131: 1518-1529
82. Heidemann J, Ogawa H, Dwinell MB, Rafiee P, Maaser C, Gockel HR, Otterson MF, Ota DM, Lugering N, Domschke W, Binion DG. Angiogenic effects of interleukin 8 (CXCL8) in human intestinal microvascular endothelial cells are mediated by CXCR2. J Biol Chem 2003; 278: 8508-8515
83. Utgaard JO, Jahnsen FL, Bakka A, Brandtzaeg P, Haraldsen G. Rapid secretion of prestored interleukin 8 from WeibelPalade bodies of microvascular en dothelial cells. J Exp Med 1998; 188: 1751-1756
84. Gijsbers K, Van Assche G, Joossens S, Struyf S, Proost P, Rutgeerts P, Geboes K, Van Damme J. CXCR1-binding chemokines in inflammatory bowel diseases: down-regulated IL-8/CXCL8 production by leukocytes in Crohn's disease and selective GCP-2/CXCL6 expression in inflamed intestinal tissue. Eur J Immunol 2004; 34: 1992-2000
85. Lügering N, Kucharzik T, Gockel H, Sorg C, Stoll R, Domschke W. Human intestinal epithelial cells down-regulate IL-8 expression in human intestinal microvascular endothelial cells; role of transforming growth factor-beta 1 (TGFbeta1). Clin Exp Immunol 1998; 114: 377-384
86. Kanazawa S, Tsunoda T, Onuma E, Majima T, Kagiyama M, Kikuchi K. VEGF, basic-FGF, and TGF-beta in Crohn's disease and ulcerative colitis: a novel mechanism of chronic intestinal inflammation. Am J Gastroenterol 2001; 96: 822-828
87. Scaldaferri F, Sans M, Vetrano S, Correale C, Arena V, Pagano N, Rando G, Romeo F, Potenza AE, Repici A, Malesci A, Danese S. The role of MAPK in governing lymphocyte adhesion to and migration across the microvasculature in inflammatory bowel disease. Eur J Immunol 2009; 39: 290-300
88. Scaldaferri F, Correale C, Gasbarrini A, Danese S. Molecular signaling blockade as a new approach to inhibit leukocyteendothelial interactions for inflammatory bowel disease treatment. Cell Adh Migr 2009; 3: 296-299
89. Imaizumi T, Yoshida H, Satoh K. Regulation of CX3CL1/ fractalkine expression in endothelial cells. J Atheroscler Thromb 2004; 11: 15-21
90. Nishimura M, Kuboi Y, Muramoto K, Kawano T, Imai T. Chemokines as novel therapeutic targets for inflammatory bowel disease. Ann N Y Acad Sci 2009; 1173: 350-356
91. Sans M, Danese S, de la Motte C, de Souza HS, Rivera-Reyes BM, West GA, Phillips M, Katz JA, Fiocchi C. Enhanced recruitment of CX3CR1+ T cells by mucosal endothelial cellderived fractalkine in inflammatory bowel disease. Gastroenterology 2007; 132: 139-153
92. Heidemann J, Ogawa H, Rafiee P, Lügering N, Maaser C, Domschke W, Binion DG, Dwinell MB. Mucosal angiogenesis regulation by CXCR4 and its ligand CXCL12 expressed by human intestinal microvascular endothelial cells. Am J Physiol Gastrointest Liver Physiol 2004; 286: G1059-G1068
93. Schober A. Chemokines in vascular dysfunction and remodeling. Arterioscler Thromb Vasc Biol 2008; 28: 1950-1959
94. Hristov M, Zernecke A, Schober A, Weber C. Adult progenitor cells in vascular remodeling during atherosclerosis. Biol Chem 2008; 389: 837-844
95. Garolla A, D'Incà R, Checchin D, Biagioli A, De Toni L, Nicoletti V, Scarpa M, Bolzonello E, Sturniolo GC, Foresta C. Reduced endothelial progenitor cell number and function in inflammatory bowel disease: a possible link to the pathogenesis. Am J Gastroenterol 2009; 104: 2500-2507
96. Ikematsu S, Yano A, Aridome K, Kikuchi M, Kumai H, Nagano H, Okamoto K, Oda M, Sakuma S, Aikou T, Muramatsu H, Kadomatsu K, Muramatsu T. Serum midkine levels are increased in patients with various types of carcinomas. Br J Cancer 2000; 83: 701-706
97. Muramatsu T. Midkine and pleiotrophin: two related proteins involved in development, survival, inflammation and tumorigenesis. J Biochem 2002; 132: 359-371
98. Qi M, Ikematsu S, Ichihara-Tanaka K, Sakuma S, Muramatsu T, Kadomatsu K. Midkine rescues Wilms' tumor cells from cisplatin-induced apoptosis: regulation of Bcl-2 expression by Midkine. J Biochem 2000; 127: 269-277
99. Krzystek-Korpacka M, Neubauer K, Matusiewicz M. Clinical relevance of circulating midkine in ulcerative colitis. Clin Chem Lab Med 2009; 47: 1085-1090
100. Tsiolakidou G, Koutroubakis IE, Tzardi M, Kouroumalis EA. Increased expression of VEGF and CD146 in patients with inflammatory bowel disease. Dig Liver Dis 2008; 40: 673-679
101. Kapsoritakis A, Sfiridaki A, Maltezos E, Simopoulos K, Giatromanolaki A, Sivridis E, Koukourakis MI. Vascular endothelial growth factor in inflammatory bowel disease. Int J Colorectal Dis 2003; 18: 418-422
102. Koizumi M, King N, Lobb R, Benjamin C, Podolsky DK. Expression of vascular adhesion molecules in inflammatory bowel disease. Gastroenterology 1992; 103: 840-847
103. Sumi Y, Muramatsu H, Takei Y, Hata K, Ueda M, Muramatsu T. Midkine, a heparin-binding growth factor, promotes growth and glycosaminoglycan synthesis of endothelial cells through its action on smooth muscle cells in an artificial blood vessel model. J Cell Sci 2002; 115: 2659-2667
104. McDonald SA, Palmen MJ, Van Rees EP, MacDonald TT. Characterization of the mucosal cell-mediated immune response in IL-2 knockout mice before and after the onset of colitis. Immunology 1997; 91: 73-80
105. Burns RC, Rivera-Nieves J, Moskaluk CA, Matsumoto S, Cominelli F, Ley K. Antibody blockade of ICAM-1 and VCAM-1 ameliorates inflammation in the SAMP-1/Yit adoptive transfer model of Crohn's disease in mice. Gastroenterology 2001; 121: 1428-1436
106. Iijima H, Neurath MF, Nagaishi T, Glickman JN, Nieuwenhuis EE, Nakajima A, Chen D, Fuss IJ, Utku N, Lewicki DN, Becker C, Gallagher TM, Holmes KV, Blumberg RS. Specific regulation of T helper cell 1-mediated murine colitis by CEACAM1. J Exp Med 2004; 199: 471-482
107. Oshima T, Pavlick KP, Laroux FS, Verma SK, Jordan P, Grisham MB, Williams L, Alexander JS. Regulation and distribution of MAdCAM-1 in endothelial cells in vitro. Am J Physiol Cell Physiol 2001; 281: C1096-C1105
108. Bardin N, Reumaux D, Geboes K, Colombel JF, Blot-Chabaud M, Sampol J, Duthilleul P, Dignat-George F. Increased expression of CD146, a new marker of the endothelial junction in active inflammatory bowel disease. Inflamm Bowel Dis 2006; 12: 16-21
109. Magro F, Araujo F, Pereira P, Meireles E, Diniz-Ribeiro M, Velosom FT. Soluble selectins, sICAM, sVCAM, and angiogenic proteins in different activity groups of patients with inflammatory bowel disease. Dig Dis Sci 2004; 49: 1265-1274
110. Newman W, Mirabelli CK. The link between inflammatory disease and patterns of leukocyte recruitment. Expert Opin Investig Drugs 1998; 7: 19-25
111. Sasaki M, Jordan P, Welbourne T, Minagar A, Joh T, Itoh M, Elrod JW, Alexander JS. Troglitazone, a PPAR-gamma activator prevents endothelial cell adhesion molecule expression and lymphocyte adhesion mediated by TNF-alpha. BMC Physiol 2005; 5: 3
112. Davenpeck KL, Gauthier TW, Albertine KH, Lefer AM. Role of P-selectin in microvascular leukocyte-endothelial interaction in splanchnic ischemia-reperfusion. Am J Physiol 1994; 267: H622-H630
113. Kobayashi M, Fukuda M, Nakayama J. Role of sulfated O-glycans expressed by high endothelial venule-like vessels in pathogenesis of chronic inflammatory gastrointestinal diseases. Biol Pharm Bull 2009; 32: 774-779
114. Rivera-Nieves J, Burcin TL, Olson TS, Morris MA, McDuffie M, Cominelli F, Ley K. Critical role of endothelial P-selectin glycoprotein ligand 1 in chronic murine ileitis. J Exp Med 2006; 203: 907-917
115. Fägerstam JP, Whiss PA. Higher platelet P-selectin in male patients with inflammatory bowel disease compared to healthy males. World J Gastroenterol 2006; 12: 1270-1272
116. Rho YH, Chung CP, Oeser A, Solus J, Asanuma Y, Sokka T, Pincus T, Raggi P, Gebretsadik T, Shintani A, Stein CM. Inflammatory mediators and premature coronary atherosclerosis in rheumatoid arthritis. Arthritis Rheum 2009; 61: 1580-1585
117. Zittermann SI, Issekutz AC. Endothelial growth factors VEGF and bFGF differentially enhance monocyte and neutrophil recruitment to inflammation. J Leukoc Biol 2006; 80: 247-257
118. Kobayashi M, Hoshino H, Masumoto J, Fukushima M, Suzawa K, Kageyama S, Suzuki M, Ohtani H, Fukuda M, Nakayama J. GlcNAc6ST-1-mediated decoration of MAd- CAM-1 protein with L-selectin ligand carbohydrates directs disease activity of ulcerative colitis. Inflamm Bowel Dis 2009; 15: 697-706
119. Briskin M, Winsor-Hines D, Shyjan A, Cochran N, Bloom S, Wilson J, McEvoy LM, Butcher EC, Kassam N, Mackay CR, Newman W, Ringler DJ. Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated lymphoid tissue. Am J Pathol 1997; 151: 97-110
120. Burgio VL, Fais S, Boirivant M, Perrone A, Pallone F. Peripheral monocyte and naive T-cell recruitment and activation in Crohn's disease. Gastroenterology 1995; 109: 1029-1038
121. Mizushima T, Sasaki M, Ando T, Wada T, Tanaka M, Okamoto Y, Ebi M, Hirata Y, Murakami K, Mizoshita T, Shimura T, Kubota E, Ogasawara N, Tanida S, Kataoka H, Kamiya T, Alexander JS, Joh T. Blockage of angiotensin II type 1 receptor regulates TNF-alpha-induced MAdCAM-1 expression via inhibition of NF-kappaB translocation to the nucleus and ameliorates colitis. Am J Physiol Gastrointest Liver Physiol 2010; 298: G255-G266
122. Alexander JS, Ando T. Density-dependent control of MAd- CAM-1 and chronic inflammation. Focus on Mechanisms of MAdCAM-1 gene expression in human intestinal microvascular endothelial cells. Am J Physiol Cell Physiol 2005; 288: C243-C244
123. Ando T, Jordan P, Wang Y, Itoh M, Joh T, Sasaki M, Elrod JW, Carpenter A, Jennings MH, Minagar A, Alexander JS. MAdCAM-1 expression and regulation in murine colonic endothelial cells in vitro. Inflamm Bowel Dis 2005; 11: 258-264
124. Lu M, Perez VL, Ma N, Miyamoto K, Peng HB, Liao JK, Adamis AP. VEGF increases retinal vascular ICAM-1 expression in vivo. Invest Ophthalmol Vis Sci 1999; 40: 1808-1812
125. Goebel S, Huang M, Davis WC, Jennings M, Siahaan TJ, Alexander JS, Kevil CG. VEGF-A stimulation of leukocyte adhesion to colonic microvascular endothelium: implications for inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol 2006; 290: G648-G654
126. Ostanin DV, Bao J, Koboziev I, Gray L, Robinson-Jackson SA, Kosloski-Davidson M, Price VH, Grisham MB. T cell transfer model of chronic colitis: concepts, considerations, and tricks of the trade. Am J Physiol Gastrointest Liver Physiol 2009; 296: G135-G146
127. Binion DG, Heidemann J, Li MS, Nelson VM, Otterson MF, Rafiee P. Vascular cell adhesion molecule-1 expression in human intestinal microvascular endothelial cells is regulated by PI 3-kinase/Akt/MAPK/NF-kappaB: inhibitory role of curcumin. Am J Physiol Gastrointest Liver Physiol 2009; 297: G259-G268
128. Kim I, Moon SO, Kim SH, Kim HJ, Koh YS, Koh GY. Vascular endothelial growth factor expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), and E-selectin through nuclear factorkappa B activation in endothelial cells. J Biol Chem 2001; 276: 7614-7620
129. Sans M, Fuster D, Vázquez A, Setoain FJ, Piera C, Piqué JM, Panés J. 123Iodine-labelled anti-VCAM-1 antibody scintigraphy in the assessment of experimental colitis. Eur J Gastroenterol Hepatol 2001; 13: 31-38
130. Soriano A, Salas A, Salas A, Sans M, Gironella M, Elena M, Anderson DC, Piqué JM, Panés J. VCAM-1, but not ICAM-1 or MAdCAM-1, immunoblockade ameliorates DSS-induced colitis in mice. Lab Invest 2000; 80: 1541-1551
131. Rijcken E, Mennigen RB, Schaefer SD, Laukoetter MG, Anthoni C, Spiegel HU, Bruewer M, Senninger N, Krieglstein CF. PECAM-1 (CD 31) mediates transendothelial leukocyte migration in experimental colitis. Am J Physiol Gastrointest Liver Physiol 2007; 293: G446-G452
132. Elshal MF, Khan SS, Raghavachari N, Takahashi Y, Barb J, Bailey JJ, Munson PJ, Solomon MA, Danner RL, McCoy JP Jr. A unique population of effector memory lymphocytes identified by CD146 having a distinct immunophenotypic and genomic profile. BMC Immunol 2007; 8: 29
133. Elshal MF, Khan SS, Takahashi Y, Solomon MA, McCoy JP Jr. CD146 (Mel-CAM), an adhesion marker of endothelial cells, is a novel marker of lymphocyte subset activation in normal peripheral blood. Blood 2005; 106: 2923-2924
134. Covas DT, Panepucci RA, Fontes AM, Silva WA Jr, Orellana MD, Freitas MC, Neder L, Santos AR, Peres LC, Jamur MC, Zago MA. Multipotent mesenchymal stromal cells obtained from diverse human tissues share functional properties and gene-expression profile with CD146+ perivascular cells and fibroblasts. Exp Hematol 2008; 36: 642-654
135. Bardin N, Blot-Chabaud M, Despoix N, Kebir A, Harhouri K, Arsanto JP, Espinosa L, Perrin P, Robert S, Vely F, Sabatier F, Le Bivic A, Kaplanski G, Sampol J, Dignat-George F. CD146 and its soluble form regulate monocyte transendothelial migration. Arterioscler Thromb Vasc Biol 2009; 29: 746-753
136. Tabibian JH, Roth BE. Local thrombolysis: a newer approach to treating inflammatory bowel disease-related thromboembolism. J Clin Gastroenterol 2009; 43: 391-398
137. Hatoum OA, Spinelli KS, Abu-Hajir M, Attila T, Franco J, Otterson MF, Telford GL, Binion DG. Mesenteric venous thrombosis in inflammatory bowel disease. J Clin Gastroenterol 2005; 39: 27-31
138. Bernstein CN, Sargent M, Vos HL, Rosendaal FR. Mutations in clotting factors and inflammatory bowel disease. Am J Gastroenterol 2007; 102: 338-343
139. Dardik R, Loscalzo J, Eskaraev R, Inbal A. Molecular mechanisms underlying the proangiogenic effect of factor XIII. Arterioscler Thromb Vasc Biol 2005; 25: 526-532
140. Vrij AA, Rijken J, van Wersch JW, Stockbrügger RW. Differential behavior of coagulation factor XIII in patients with inflammatory bowel disease and in patients with giant cell arteritis. Haemostasis 1999; 29: 326-335
141. Danese S, Katz JA, Saibeni S, Papa A, Gasbarrini A, Vecchi M, Fiocchi C. Activated platelets are the source of elevated levels of soluble CD40 ligand in the circulation of inflammatory bowel disease patients. Gut 2003; 52: 1435-1441
142. Danese S, de la Motte C, Sturm A, Vogel JD, West GA, Strong SA, Katz JA, Fiocchi C. Platelets trigger a CD40-dependent inflammatory response in the microvasculature of inflammatory bowel disease patients. Gastroenterology 2003; 124: 1249-1264
143. Vogel JD, West GA, Danese S, De La Motte C, Phillips MH, Strong SA, Willis J, Fiocchi C. CD40-mediated immunenonimmune cell interactions induce mucosal fibroblast chemokines leading to T-cell transmigration. Gastroenterology 2004; 126: 63-80
144. Srirajaskanthan R, Winter M, Muller AF. Venous thrombosis in inflammatory bowel disease. Eur J Gastroenterol Hepatol 2005; 17: 697-700
145. Hathaway CA, Appleyard CB, Percy WH, Williams JL. Experimental colitis increases blood-brain barrier permeability in rabbits. Am J Physiol 1999; 276: G1174-G1180
146. Koutroubakis IE, Xidakis C, Karmiris K, Sfiridaki A, Kandidaki E, Kouroumalis EA. Serum angiogenin in inflammatory bowel disease. Dig Dis Sci 2004; 49: 1758-1762
147. Im E, Choi YJ, Kim CH, Fiocchi C, Pothoulakis C, Rhee SH. The angiogenic effect of probiotic Bacillus polyfermenticus on human intestinal microvascular endothelial cells is mediated by IL-8. Am J Physiol Gastrointest Liver Physiol 2009; 297: G999-G1008
148. Roessner A, Kuester D, Malfertheiner P, Schneider-Stock R. Oxidative stress in ulcerative colitis-associated carcinogenesis. Pathol Res Pract 2008; 204: 511-524
149. Tolstanova G, Khomenko T, Deng X, Chen L, Tarnawski A, Ahluwalia A, Szabo S, Sandor Z. Neutralizing anti-vascular endothelial growth factor (VEGF) antibody reduces severity of experimental ulcerative colitis in rats: direct evidence for the pathogenic role of VEGF. J Pharmacol Exp Ther 2009; 328: 749-757
150. Alexander J. Extracellular matrix, junctional integrity and matrix metalloproteinase interactions. J Anat 2002; 200: 525
151. Allport JR, Muller WA, Luscinskas FW. Monocytes induce reversible focal changes in vascular endothelial cadherin complex during transendothelial migration under flow. J Cell Biol 2000; 148: 203-216
152. Weber C, Fraemohs L, Dejana E. The role of junctional adhesion molecules in vascular inflammation. Nat Rev Immunol 2007; 7: 467-477
153. Meijer MJ, Mieremet-Ooms MA, van der Zon AM, van Duijn W, van Hogezand RA, Sier CF, Hommes DW, Lamers CB, Verspaget HW. Increased mucosal matrix metalloproteinase- 1, -2, -3 and -9 activity in patients with inflammatory bowel disease and the relation with Crohn's disease phenotype. Dig Liver Dis 2007; 39: 733-739
154. Mosnier JF, Jarry A, Bou-Hanna C, Denis MG, Merlin D, Laboisse CL. ADAM15 upregulation and interaction with multiple binding partners in inflammatory bowel disease. Lab Invest 2006; 86: 1064-1073
155. Alexander JS, Zhu Y, Elrod JW, Alexander B, Coe L, Kalogeris TJ, Fuseler J. Reciprocal regulation of endothelial substrate adhesion and barrier function. Microcirculation 2001; 8: 389-401
156. Carden D, Xiao F, Moak C, Willis BH, Robinson-Jackson S, Alexander S. Neutrophil elastase promotes lung microvascular injury and proteolysis of endothelial cadherins. Am J Physiol 1998; 275: H385-H392
157. Orlova VV, Economopoulou M, Lupu F, Santoso S, Chavakis T. Junctional adhesion molecule-C regulates vascular endothelial permeability by modulating VE-cadherin-mediated cell-cell contacts. J Exp Med 2006; 203: 2703-2714
158. Spalinger J, Patriquin H, Miron MC, Marx G, Herzog D, Dubois J, Dubinsky M, Seidman EG. Doppler US in patients with crohn disease: vessel density in the diseased bowel reflects disease activity. Radiology 2000; 217: 787-791
159. Danese S, Sans M, de la Motte C, Graziani C, West G, Phillips MH, Pola R, Rutella S, Willis J, Gasbarrini A, Fiocchi C. Angiogenesis as a novel component of inflammatory bowel disease pathogenesis. Gastroenterology 2006; 130: 2060-2073
160. Danese S, Papa A, Saibeni S, Repici A, Malesci A, Vecchi M. Inflammation and coagulation in inflammatory bowel disease: The clot thickens. Am J Gastroenterol 2007; 102: 174-186
161. Wakefield AJ, Sankey EA, Dhillon AP, Sawyerr AM, More L, Sim R, Pittilo RM, Rowles PM, Hudson M, Lewis AA. Granulomatous vasculitis in Crohn's disease. Gastroenterology 1991; 100: 1279-1287
162. Ginnan R, Guikema BJ, Halligan KE, Singer HA, Jourd'heuil D. Regulation of smooth muscle by inducible nitric oxide synthase and NADPH oxidase in vascular proliferative diseases. Free Radic Biol Med 2008; 44: 1232-1245
163. Ganta VC, Cromer W, Mills GL, Traylor J, Jennings M, Daley S, Clark B, Mathis JM, Bernas M, Boktor M, Jordan P, Witte M, Alexander JS. Angiopoietin-2 in experimental colitis. Inflamm Bowel Dis 2010; 16: 1029-1039
164. Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 1989; 96: 795-803
165. Peterson TC, Cleary CE, Shaw AM, Malatjalian DA, Veldhuyzen van Zanten SJ. Therapeutic role for bismuth compounds in TNBS-induced colitis in the rat. Dig Dis Sci 2000; 45: 466-473
166. Chidlow JH Jr, Langston W, Greer JJ, Ostanin D, Abdelbaqi M, Houghton J, Senthilkumar A, Shukla D, Mazar AP, Grisham MB, Kevil CG. Differential angiogenic regulation of experimental colitis. Am J Pathol 2006; 169: 2014-2030
167. Scaldaferri F, Vetrano S, Sans M, Arena V, Straface G, Stigliano E, Repici A, Sturm A, Malesci A, Panes J, Yla-Herttuala S, Fiocchi C, Danese S. VEGF-A links angiogenesis and inflammation in inflammatory bowel disease pathogenesis. Gastroenterology 2009; 136: 585-595.e5
168. Kenet G, Wardi J, Avni Y, Aeed H, Shirin H, Zaidel L, Hershkoviz R, Bruck R. Amelioration of experimental colitis by thalidomide. Isr Med Assoc J 2001; 3: 644-648
169. Maconi G, Sampietro GM, Russo A, Bollani S, Cristaldi M, Parente F, Dottorini F, Bianchi Porro G. The vascularity of internal fistulae in Crohn's disease: an in vivo power Doppler ultrasonography assessment. Gut 2002; 50: 496-500
170. Wallace JL, Le T, Carter L, Appleyard CB, Beck PL. Hapteninduced chronic colitis in the rat: alternatives to trinitrobenzene sulfonic acid. J Pharmacol Toxicol Methods 1995; 33: 237-239
171. Funayama Y, Sasaki I, Naito H, Fukushima K, Matsuno S, Masuda T. Remodeling of vascular wall in Crohn's disease. Dig Dis Sci 1999; 44: 2319-2323
172. Angerson WJ, Allison MC, Baxter JN, Russell RI. Neoterminal ileal blood flow after ileocolonic resection for Crohn's disease. Gut 1993; 34: 1531-1534
173. Olsson AK, Dimberg A, Kreuger J, Claesson-Welsh L. VEGF receptor signalling - in control of vascular function. Nat Rev Mol Cell Biol 2006; 7: 359-371
174. Usui T, Ishida S, Yamashiro K, Kaji Y, Poulaki V, Moore J, Moore T, Amano S, Horikawa Y, Dartt D, Golding M, Shima DT, Adamis AP. VEGF164(165) as the pathological isoform: differential leukocyte and endothelial responses through VEGFR1 and VEGFR2. Invest Ophthalmol Vis Sci 2004; 45: 368-374
175. Bousvaros A, Leichtner A, Zurakowski D, Kwon J, Law T, Keough K, Fishman S. Elevated serum vascular endothelial growth factor in children and young adults with Crohn's disease. Dig Dis Sci 1999; 44: 424-430
176. Ozawa CR, Banfi A, Glazer NL, Thurston G, Springer ML, Kraft PE, McDonald DM, Blau HM. Microenvironmental VEGF concentration, not total dose, determines a threshold between normal and aberrant angiogenesis. J Clin Invest 2004; 113: 516-527
177. Danese S, Sans M, Spencer DM, Beck I, Doñate F, Plunkett ML, de la Motte C, Redline R, Shaw DE, Levine AD, Mazar AP, Fiocchi C. Angiogenesis blockade as a new therapeutic approach to experimental colitis. Gut 2007; 56: 855-862
178. Appleton I, Brown NJ, Willis D, Colville-Nash PR, Alam C, Brown JR, Willoughby DA. The role of vascular endothelial growth factor in a murine chronic granulomatous tissue air pouch model of angiogenesis. J Pathol 1996; 180: 90-94
179. Edelman JL, Castro MR, Wen Y. Correlation of VEGF expression by leukocytes with the growth and regression of blood vessels in the rat cornea. Invest Ophthalmol Vis Sci 1999; 40: 1112-1123
180. Petersen W, Tsokos M, Pufe T. Expression of VEGF121 and VEGF165 in hypertrophic chondrocytes of the human growth plate and epiphyseal cartilage. J Anat 2002; 201: 153-157
181. Lu J, Kasama T, Kobayashi K, Yoda Y, Shiozawa F, Hanyuda M, Negishi M, Ide H, Adachi M. Vascular endothelial growth factor expression and regulation of murine collageninduced arthritis. J Immunol 2000; 164: 5922-5927
182. Kevil CG, De Benedetti A, Payne DK, Coe LL, Laroux FS, Alexander JS. Translational regulation of vascular permeability factor by eukaryotic initiation factor 4E: implications for tumor angiogenesis. Int J Cancer 1996; 65: 785-790
183. Griga T, Gutzeit A, Sommerkamp C, May B. Increased production of vascular endothelial growth factor by peripheral blood mononuclear cells in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol 1999; 11: 175-179
184. Birmingham JM, Busik JV, Hansen-Smith FM, Fenton JI. Novel mechanism for obesity-induced colon cancer progression. Carcinogenesis 2009; 30: 690-697
185. Kusumanto YH, Dam WA, Hospers GA, Meijer C, Mulder NH. Platelets and granulocytes, in particular the neutrophils, form important compartments for circulating vascular endothelial growth factor. Angiogenesis 2003; 6: 283-287
186. Kucharzik T, Walsh SV, Chen J, Parkos CA, Nusrat A. Neutrophil transmigration in inflammatory bowel disease is associated with differential expression of epithelial intercellular junction proteins. Am J Pathol 2001; 159: 2001-2009
187. Perminow G, Reikvam DH, Lyckander LG, Brandtzaeg P, Vatn MH, Carlsen HS. Increased number and activation of colonic macrophages in pediatric patients with untreated Crohn's disease. Inflamm Bowel Dis 2009; 15: 1368-1378
188. Upile T, Jerjes W, Kafas P, Harini S, Singh SU, Guyer M, Bentley M, Sudhoff H, Hopper C. Salivary VEGF: a noninvasive angiogenic and lymphangiogenic proxy in head and neck cancer prognostication. Int Arch Med 2009; 2: 12
189. Krzystek-Korpacka M, Neubauer K, Matusiewicz M. Platelet- derived growth factor-BB reflects clinical, inflammatory and angiogenic disease activity and oxidative stress in inflammatory bowel disease. Clin Biochem 2009; 42: 1602-1609
190. Del Zotto B, Mumolo G, Pronio AM, Montesani C, Tersigni R, Boirivant M. TGF-beta1 production in inflammatory bowel disease: differing production patterns in Crohn's disease and ulcerative colitis. Clin Exp Immunol 2003; 134: 120-126
191. Beck PL, Podolsky DK. Growth factors in inflammatory bowel disease. Inflamm Bowel Dis 1999; 5: 44-60
192. Ma Y, Guan Q, Bai A, Weiss CR, Hillman CL, Ma A, Zhou G, Qing G, Peng Z. Targeting TGF-beta1 by employing a vaccine ameliorates fibrosis in a mouse model of chronic colitis. Inflamm Bowel Dis 2010; 16: 1040-1050
193. Rieder F, Fiocchi C. Intestinal fibrosis in IBD--a dynamic, multifactorial process. Nat Rev Gastroenterol Hepatol 2009; 6: 228-235
194. Zeisberg EM, Tarnavski O, Zeisberg M, Dorfman AL, Mc-Mullen JR, Gustafsson E, Chandraker A, Yuan X, Pu WT, Roberts AB, Neilson EG, Sayegh MH, Izumo S, Kalluri R. Endothelial-to-mesenchymal transition contributes to cardiac fibrosis. Nat Med 2007; 13: 952-961
195. Sundberg C, Ivarsson M, Gerdin B, Rubin K. Pericytes as collagen-producing cells in excessive dermal scarring. Lab Invest 1996; 74: 452-466
196. Bousvaros A, Zurakowski D, Fishman SJ, Keough K, Law T, Sun C, Leichtner AM. Serum basic fibroblast growth factor in pediatric Crohn's disease. Implications for wound healing. Dig Dis Sci 1997; 42: 378-386
197. Mannaioni PF, Di Bello MG, Masini E. Platelets and inflammation: role of platelet-derived growth factor, adhesion molecules and histamine. Inflamm Res 1997; 46: 4-18
198. Di Lorenzo A, Fernández-Hernando C, Cirino G, Sessa WC. Akt1 is critical for acute inflammation and histaminemediated vascular leakage. Proc Natl Acad Sci USA 2009; 106: 14552-14557
199. Dulic-Sills A, Blunden MJ, Mawdsley J, Bastin AJ, McAuley D, Griffiths M, Rampton DS, Yaqoob MM, Macey MG, Agrawal SG. New flow cytometric technique for the evaluation of circulating endothelial progenitor cell levels in various disease groups. J Immunol Methods 2006; 316: 107-115
200. Jakobsson L, Bentley K, Gerhardt H. VEGFRs and Notch: a dynamic collaboration in vascular patterning. Biochem Soc Trans 2009; 37: 1233-1236
201. Gerhardt H, Golding M, Fruttiger M, Ruhrberg C, Lundkvist A, Abramsson A, Jeltsch M, Mitchell C, Alitalo K, Shima D, Betsholtz C. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol 2003; 161: 1163-1177
202. Imhof BA, Aurrand-Lions M. Angiogenesis and inflammation face off. Nat Med 2006; 12: 171-172
203. Fiedler U, Augustin HG. Angiopoietins: a link between angiogenesis and inflammation. Trends Immunol 2006; 27: 552-558
204. Fiedler U, Scharpfenecker M, Koidl S, Hegen A, Grunow V, Schmidt JM, Kriz W, Thurston G, Augustin HG. The Tie-2 ligand angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies. Blood 2004; 103: 4150-4156
205. Fujiyama S, Matsubara H, Nozawa Y, Maruyama K, Mori Y, Tsutsumi Y, Masaki H, Uchiyama Y, Koyama Y, Nose A, Iba O, Tateishi E, Ogata N, Jyo N, Higashiyama S, Iwasaka T. Angiotensin AT(1) and AT(2) receptors differentially regulate angiopoietin-2 and vascular endothelial growth factor expression and angiogenesis by modulating heparin binding-epidermal growth factor (EGF)-mediated EGF receptor transactivation. Circ Res 2001; 88: 22-29
206. Chen YH, Wu HL, Chen CK, Huang YH, Yang BC, Wu LW. Angiostatin antagonizes the action of VEGF-A in human endothelial cells via two distinct pathways. Biochem Biophys Res Commun 2003; 310: 804-810
207. Sandor Z, Deng XM, Khomenko T, Tarnawski AS, Szabo S. Altered angiogenic balance in ulcerative colitis: a key to impaired healing? Biochem Biophys Res Commun 2006; 350: 147-150
208. Cornelius LA, Nehring LC, Harding E, Bolanowski M, Welgus HG, Kobayashi DK, Pierce RA, Shapiro SD. Matrix metalloproteinases generate angiostatin: effects on neovascularization. J Immunol 1998; 161: 6845-6852
209. Folkman J. Antiangiogenesis in cancer therapy-endostatin and its mechanisms of action. Exp Cell Res 2006; 312: 594-607
210. Deng X, Tolstanova G, Khomenko T, Chen L, Tarnawski A, Szabo S, Sandor Z. Mesalamine restores angiogenic balance in experimental ulcerative colitis by reducing expression of endostatin and angiostatin: novel molecular mechanism for therapeutic action of mesalamine. J Pharmacol Exp Ther 2009; 331: 1071-1078
211. Ambati BK, Nozaki M, Singh N, Takeda A, Jani PD, Suthar T, Albuquerque RJ, Richter E, Sakurai E, Newcomb MT, Kleinman ME, Caldwell RB, Lin Q, Ogura Y, Orecchia A, Samuelson DA, Agnew DW, St Leger J, Green WR, Mahasreshti PJ, Curiel DT, Kwan D, Marsh H, Ikeda S, Leiper LJ, Collinson JM, Bogdanovich S, Khurana TS, Shibuya M, Baldwin ME, Ferrara N, Gerber HP, De Falco S, Witta J, Baffi JZ, Raisler BJ, Ambati J. Corneal avascularity is due to soluble VEGF receptor-1. Nature 2006; 443: 993-997
212. Ambati BK, Patterson E, Jani P, Jenkins C, Higgins E, Singh N, Suthar T, Vira N, Smith K, Caldwell R. Soluble vascular endothelial growth factor receptor-1 contributes to the corneal antiangiogenic barrier. Br J Ophthalmol 2007; 91: 505-508
213. Albuquerque RJ, Hayashi T, Cho WG, Kleinman ME, Dridi S, Takeda A, Baffi JZ, Yamada K, Kaneko H, Green MG, Chappell J, Wilting J, Weich HA, Yamagami S, Amano S, Mizuki N, Alexander JS, Peterson ML, Brekken RA, Hirashima M, Capoor S, Usui T, Ambati BK, Ambati J. Alternatively spliced vascular endothelial growth factor receptor-2 is an essential endogenous inhibitor of lymphatic vessel growth. Nat Med 2009; 15: 1023-1030
214. Bates DO, Cui TG, Doughty JM, Winkler M, Sugiono M, Shields JD, Peat D, Gillatt D, Harper SJ. VEGF165b, an inhibitory splice variant of vascular endothelial growth factor, is down-regulated in renal cell carcinoma. Cancer Res 2002; 62: 4123-4131
215. Perrin RM, Konopatskaya O, Qiu Y, Harper S, Bates DO, Churchill AJ. Diabetic retinopathy is associated with a switch in splicing from anti- to pro-angiogenic isoforms of vascular endothelial growth factor. Diabetologia 2005; 48: 2422-2427
216. Varey AH, Rennel ES, Qiu Y, Bevan HS, Perrin RM, Raffy S, Dixon AR, Paraskeva C, Zaccheo O, Hassan AB, Harper SJ, Bates DO. VEGF 165 b, an antiangiogenic VEGF-A isoform, binds and inhibits bevacizumab treatment in experimental colorectal carcinoma: balance of pro- and antiangiogenic VEGF-A isoforms has implications for therapy. Br J Cancer 2008; 98: 1366-1379
217. Nowak DG, Woolard J, Amin EM, Konopatskaya O, Saleem MA, Churchill AJ, Ladomery MR, Harper SJ, Bates DO. Expression of pro- and anti-angiogenic isoforms of VEGF is differentially regulated by splicing and growth factors. J Cell Sci 2008; 121: 3487-3495
218. Leong TT, Fearon U, Veale DJ. Angiogenesis in psoriasis and psoriatic arthritis: clues to disease pathogenesis. Curr Rheumatol Rep 2005; 7: 325-329
219. Veale DJ, Fearon U. Inhibition of angiogenic pathways in rheumatoid arthritis: potential for therapeutic targeting. Best Pract Res Clin Rheumatol 2006; 20: 941-947
220. Cordiali-Fei P, Trento E, D'Agosto G, Bordignon V, Mussi A, Ardigó M, Mastroianni A, Vento A, Solivetti F, Berardesca E, Ensoli F. Effective therapy with anti-TNF-alpha in patients with psoriatic arthritis is associated with decreased levels of metalloproteinases and angiogenic cytokines in the sera and skin lesions. Ann N Y Acad Sci 2007; 1110: 578-589
221. Siegmund B. Targeted therapies in inflammatory bowel disease. Dig Dis 2009; 27: 465-469
222. Rafiee P, Heidemann J, Ogawa H, Johnson NA, Fisher PJ, Li MS, Otterson MF, Johnson CP, Binion DG. Cyclosporin A differentially inhibits multiple steps in VEGF induced angiogenesis in human microvascular endothelial cells through altered intracellular signaling. Cell Commun Signal 2004; 2: 3
223. Carvalho AT, Souza H, Carneiro AJ, Castelo-Branco M, Madi K, Schanaider A, Silv F, Pereira Jr FA, Pereira MG, Tortori C, Dines I, Carvalho J, Rocha E, Elia C. Therapeutic and prophylactic thalidomide in TNBS-induced colitis: synergistic effects on TNF-alpha, IL-12 and VEGF production. World J Gastroenterol 2007; 13: 2166-2173
224. Ogawa H, Rafiee P, Fisher PJ, Johnson NA, Otterson MF, Binion DG. Butyrate modulates gene and protein expression in human intestinal endothelial cells. Biochem Biophys Res Commun 2003; 309: 512-519
225. Kruh J, Defer N, Tichonicky L. [Molecular and cellular action of butyrate] C R Seances Soc Biol Fil 1992; 186: 12-25
226. Ogawa H, Rafiee P, Fisher PJ, Johnson NA, Otterson MF, Binion DG. Sodium butyrate inhibits angiogenesis of human intestinal microvascular endothelial cells through COX-2 inhibition. FEBS Lett 2003; 554: 88-94
227. Rafiee P, Stein DJ, Nelson VM, Otterson MF, Shaker R, Binion DG. Thalidomide inhibits inflammatory and angiogenic activation of human intestinal microvascular endothelial cells (HIMEC). Am J Physiol Gastrointest Liver Physiol 2010; 298: G167-G176
228. Rafiee P, Johnson CP, Li MS, Ogawa H, Heidemann J, Fisher PJ, Lamirand TH, Otterson MF, Wilson KT, Binion DG. Cyclosporine A enhances leukocyte binding by human intestinal microvascular endothelial cells through inhibition of p38 MAPK and iNOS. Paradoxical proinflammatory effect on the microvascular endothelium. J Biol Chem 2002; 277: 35605-35615
229. Choi PM, Zelig MP. Similarity of colorectal cancer in Crohn's disease and ulcerative colitis: implications for carcinogenesis and prevention. Gut 1994; 35: 950-954
230. Karlén P, Löfberg R, Broström O, Leijonmarck CE, Hellers G, Persson PG. Increased risk of cancer in ulcerative colitis: a population-based cohort study. Am J Gastroenterol 1999; 94: 1047-1052
231. Gyde SN, Prior P, Allan RN, Stevens A, Jewell DP, Truelove SC, Lofberg R, Brostrom O, Hellers G. Colorectal cancer in ulcerative colitis: a cohort study of primary referrals from three centres. Gut 1988; 29: 206-217
232. Wagner AD, Arnold D, Grothey AA, Haerting J, Unverzagt S. Anti-angiogenic therapies for metastatic colorectal cancer. Cochrane Database Syst Rev 2009; CD005392
233. Sonoshita M, Takaku K, Oshima M, Sugihara K, Taketo MM. Cyclooxygenase-2 expression in fibroblasts and endothelial cells of intestinal polyps. Cancer Res 2002; 62: 6846-6849
234. Oshima M, Dinchuk JE, Kargman SL, Oshima H, Hancock B, Kwong E, Trzaskos JM, Evans JF, Taketo MM. Suppression of intestinal polyposis in Apc delta716 knockout mice by inhibition of cyclooxygenase 2 (COX-2). Cell 1996; 87: 803-809
235. Oshima M, Taketo MM. COX selectivity and animal models for colon cancer. Curr Pharm Des 2002; 8: 1021-1034
236. Paiotti AP, Miszputen SJ, Oshima CT, de Oliveira Costa H, Ribeiro DA, Franco M. Effect of COX-2 inhibitor after TNBSinduced colitis in Wistar rats. J Mol Histol 2009; 40: 317-324
237. Binion DG, Otterson MF, Rafiee P. Curcumin inhibits VEGFmediated angiogenesis in human intestinal microvascular endothelial cells through COX-2 and MAPK inhibition. Gut 2008; 57: 1509-1517
238. Klenke FM, Gebhard MM, Ewerbeck V, Abdollahi A, Huber PE, Sckell A. The selective Cox-2 inhibitor Celecoxib suppresses angiogenesis and growth of secondary bone tumors: an intravital microscopy study in mice. BMC Cancer 2006; 6: 9
239. Chan AT. Can aspirin prevent colorectal cancer? Lancet 2007; 369: 1577-1578
240. Chan AT, Ogino S, Fuchs CS. Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N Engl J Med 2007; 356: 2131-2142
241. Park YS. [COX-2 inhibitors in inflammatory bowel disease: friends or foes?] Korean J Gastroenterol 2007; 50: 350-355
242. Wu AW, Gu J, Li ZF, Ji JF, Xu GW. COX-2 expression and tumor angiogenesis in colorectal cancer. World J Gastroenterol 2004; 10: 2323-2326
243. Ishikawa TO, Herschman HR. Tumor formation in a mouse model of colitis-associated colon cancer does not require COX-1 or COX-2 expression. Carcinogenesis 2010; 31: 729-736
244. Toomey DP, Murphy JF, Conlon KC. COX-2, VEGF and tumour angiogenesis. Surgeon 2009; 7: 174-180