Angiopoietin-2 in experimental colitis

Vijay C. Ganta, Walter Cromer, Ginny L. Mills, James Traylor, Merilyn Jennings, Sarah Daley, Benjamin Clark, James Michael Mathis, Michael Bernas, Moheb Boktor, Paul Jordan, Marlys Witte, J. Steven Alexander

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Abstract

Background: The pathophysiology of inflammatory bowel disease (IBD) includes leukocyte infiltration, blood and lymphatic remodeling, weight loss and protein enteropathy. The roles of angiopoietin-2 (Ang-2) in initiating gut inflammation, leukocyte infiltration and angiogenesis are not well understood. Methods: Disease activity index, histopathological scoring, myeloperoxidase assay, immunohistochemistry and sodium dodecyl sulphate-polyacrylamide gel electrophoretic methods were employed in the present study to addess the roles of Ang-2 in experimental colitis. Results: Several important differences were seen in the development of experimental IBD in Ang-2-/- mice. Although weight change and disease activity differ only slightly in WT and Ang-2-/- + DSS treated mice, leukocyte infiltration, inflammation and blood and lymphatic vessel density is significantly attenuated compared to WT + DSS mice. Gut capillary fragility and water export (stool blood and form) appear significantly earlier in Ang-2-/- + DSS mice vs. WT. Colon lengths were also significantly reduced in Ang-2-/- and gut histopathology was less severe in Ang-2-/- compared to WT + DSS. Lastly, the decrease in serum protein content in WT + DSS was less severe in Ang-2-/- + DSS, thus protein losing enteropathy (PLE) a feature of IBD is relieved by Ang-2-/-. Conclusion: These data demonstrate that in DSS colitis, Ang-2 mediates inflammatory hemangiogenesis, lymphangiogenesis and neutrophil infiltration to reduce some, but not all clinical features of IBD. The implications for Ang-2 manipulation in the development of IBD and other inflammatory diseases and treatments involving Ang-2 are discussed.

Original languageEnglish
Pages (from-to)1029-1039
Number of pages11
JournalInflammatory Bowel Diseases
Volume16
Issue number6
DOIs
StatePublished - 31 May 2010

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Angiopoietin-2
Colitis
Inflammatory Bowel Diseases
Leukocytes
Capillary Fragility
Protein-Losing Enteropathies
Lymphangiogenesis
Inflammation
Lymphatic Vessels
Neutrophil Infiltration
Sodium Dodecyl Sulfate
Peroxidase
Blood Vessels
Blood Proteins
Weight Loss

Keywords

  • Crohn's disease
  • MECA-32
  • Neutrophils
  • Ulcerative colitis
  • VEGFR-3

Cite this

Ganta, V. C., Cromer, W., Mills, G. L., Traylor, J., Jennings, M., Daley, S., ... Alexander, J. S. (2010). Angiopoietin-2 in experimental colitis. Inflammatory Bowel Diseases, 16(6), 1029-1039. https://doi.org/10.1002/ibd.21150
Ganta, Vijay C. ; Cromer, Walter ; Mills, Ginny L. ; Traylor, James ; Jennings, Merilyn ; Daley, Sarah ; Clark, Benjamin ; Mathis, James Michael ; Bernas, Michael ; Boktor, Moheb ; Jordan, Paul ; Witte, Marlys ; Alexander, J. Steven. / Angiopoietin-2 in experimental colitis. In: Inflammatory Bowel Diseases. 2010 ; Vol. 16, No. 6. pp. 1029-1039.
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abstract = "Background: The pathophysiology of inflammatory bowel disease (IBD) includes leukocyte infiltration, blood and lymphatic remodeling, weight loss and protein enteropathy. The roles of angiopoietin-2 (Ang-2) in initiating gut inflammation, leukocyte infiltration and angiogenesis are not well understood. Methods: Disease activity index, histopathological scoring, myeloperoxidase assay, immunohistochemistry and sodium dodecyl sulphate-polyacrylamide gel electrophoretic methods were employed in the present study to addess the roles of Ang-2 in experimental colitis. Results: Several important differences were seen in the development of experimental IBD in Ang-2-/- mice. Although weight change and disease activity differ only slightly in WT and Ang-2-/- + DSS treated mice, leukocyte infiltration, inflammation and blood and lymphatic vessel density is significantly attenuated compared to WT + DSS mice. Gut capillary fragility and water export (stool blood and form) appear significantly earlier in Ang-2-/- + DSS mice vs. WT. Colon lengths were also significantly reduced in Ang-2-/- and gut histopathology was less severe in Ang-2-/- compared to WT + DSS. Lastly, the decrease in serum protein content in WT + DSS was less severe in Ang-2-/- + DSS, thus protein losing enteropathy (PLE) a feature of IBD is relieved by Ang-2-/-. Conclusion: These data demonstrate that in DSS colitis, Ang-2 mediates inflammatory hemangiogenesis, lymphangiogenesis and neutrophil infiltration to reduce some, but not all clinical features of IBD. The implications for Ang-2 manipulation in the development of IBD and other inflammatory diseases and treatments involving Ang-2 are discussed.",
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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 2010, 'Angiopoietin-2 in experimental colitis', Inflammatory Bowel Diseases, vol. 16, no. 6, pp. 1029-1039. https://doi.org/10.1002/ibd.21150

Angiopoietin-2 in experimental colitis. / Ganta, Vijay C.; Cromer, Walter; Mills, Ginny L.; Traylor, James; Jennings, Merilyn; Daley, Sarah; Clark, Benjamin; Mathis, James Michael; Bernas, Michael; Boktor, Moheb; Jordan, Paul; Witte, Marlys; Alexander, J. Steven.

In: Inflammatory Bowel Diseases, Vol. 16, No. 6, 31.05.2010, p. 1029-1039.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Angiopoietin-2 in experimental colitis

AU - Ganta, Vijay C.

AU - Cromer, Walter

AU - Mills, Ginny L.

AU - Traylor, James

AU - Jennings, Merilyn

AU - Daley, Sarah

AU - Clark, Benjamin

AU - Mathis, James Michael

AU - Bernas, Michael

AU - Boktor, Moheb

AU - Jordan, Paul

AU - Witte, Marlys

AU - Alexander, J. Steven

PY - 2010/5/31

Y1 - 2010/5/31

N2 - Background: The pathophysiology of inflammatory bowel disease (IBD) includes leukocyte infiltration, blood and lymphatic remodeling, weight loss and protein enteropathy. The roles of angiopoietin-2 (Ang-2) in initiating gut inflammation, leukocyte infiltration and angiogenesis are not well understood. Methods: Disease activity index, histopathological scoring, myeloperoxidase assay, immunohistochemistry and sodium dodecyl sulphate-polyacrylamide gel electrophoretic methods were employed in the present study to addess the roles of Ang-2 in experimental colitis. Results: Several important differences were seen in the development of experimental IBD in Ang-2-/- mice. Although weight change and disease activity differ only slightly in WT and Ang-2-/- + DSS treated mice, leukocyte infiltration, inflammation and blood and lymphatic vessel density is significantly attenuated compared to WT + DSS mice. Gut capillary fragility and water export (stool blood and form) appear significantly earlier in Ang-2-/- + DSS mice vs. WT. Colon lengths were also significantly reduced in Ang-2-/- and gut histopathology was less severe in Ang-2-/- compared to WT + DSS. Lastly, the decrease in serum protein content in WT + DSS was less severe in Ang-2-/- + DSS, thus protein losing enteropathy (PLE) a feature of IBD is relieved by Ang-2-/-. Conclusion: These data demonstrate that in DSS colitis, Ang-2 mediates inflammatory hemangiogenesis, lymphangiogenesis and neutrophil infiltration to reduce some, but not all clinical features of IBD. The implications for Ang-2 manipulation in the development of IBD and other inflammatory diseases and treatments involving Ang-2 are discussed.

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Ganta VC, Cromer W, Mills GL, Traylor J, Jennings M, Daley S et al. Angiopoietin-2 in experimental colitis. Inflammatory Bowel Diseases. 2010 May 31;16(6):1029-1039. https://doi.org/10.1002/ibd.21150