VEGF-A isoform modulation in an preclinical TNBS model of ulcerative colitis

Protective effects of a VEGF164b therapy

Walter E. Cromer, Chaitanya V. Ganta, Mihir Patel, James Traylor, Christopher G. Kevil, J. S. Alexander, James Michael Mathis

Research output: Contribution to journalArticleResearchpeer-review

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Abstract

Background: Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the USA. A key component of UC is the increase in inflammatory angiogenesis of the colon during active disease. This increase is driven to a great extent by the over expression of VEGF-A. Recently, VEGF165b (VEGF164b in mouse), an anti-angiogenic form of VEGF-A was described and its regulation was determined to be disturbed in many pathologies such as cancer and pre-eclampsia. Results: The aims of this study were to examine the role of this inhibitory VEGF by expressing this molecule in a model of intestinal inflammation, and to evaluate its expression as a potential new therapeutic approach for treating UC. A modified model of TNBS colitis was used to determine the effects of rVEGF164b expression on colon inflammation. Expansion of the vascular system was assessed by immunhistochemical methods and macro- and microscopic measurements of inflammation in the colon were measured. Leukocyte invasion of the tissue was measured by myeloperoxidase assay and identification and counting of lymphoid follicles. Both angio- and lymphangiogenesis were reduced by expression of rVEGF164b, which correlated with reduction in both gross and microscopic inflammatory scores. Leukocyte invasion of the tissue was also reduced by rVEGF164b expression. Conclusions: This is the first report using an endogenous inhibitory VEGF-A isoform for therapy in a model of experimental colitis. Inhibitory VEGF molecules play an important role in maintenance of gut homeostasis and may be dysregulated in UC. The results of this study suggest that restoration of rVEGF164b expression has anti-inflammatory activity in a TNBS model and warrants further examination as a possible therapeutic for UC.

Original languageEnglish
Article number207
JournalJournal of Translational Medicine
Volume11
Issue number1
DOIs
StatePublished - 11 Sep 2013

Fingerprint

Ulcerative Colitis
Vascular Endothelial Growth Factor A
Protein Isoforms
Modulation
Colon
Colitis
Inflammation
Leukocytes
Tissue
Lymphangiogenesis
Therapeutics
Molecules
Pathology
Pre-Eclampsia
Inflammatory Bowel Diseases
Peroxidase
Restoration
Blood Vessels
Macros
Assays

Keywords

  • Adenovirus
  • Angiogenesis
  • Colon
  • Inflammation
  • TNBS
  • Therapy
  • Ulcerative colitis
  • VEGF

Cite this

Cromer, Walter E. ; Ganta, Chaitanya V. ; Patel, Mihir ; Traylor, James ; Kevil, Christopher G. ; Alexander, J. S. ; Mathis, James Michael. / VEGF-A isoform modulation in an preclinical TNBS model of ulcerative colitis : Protective effects of a VEGF164b therapy. In: Journal of Translational Medicine. 2013 ; Vol. 11, No. 1.
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title = "VEGF-A isoform modulation in an preclinical TNBS model of ulcerative colitis: Protective effects of a VEGF164b therapy",
abstract = "Background: Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the USA. A key component of UC is the increase in inflammatory angiogenesis of the colon during active disease. This increase is driven to a great extent by the over expression of VEGF-A. Recently, VEGF165b (VEGF164b in mouse), an anti-angiogenic form of VEGF-A was described and its regulation was determined to be disturbed in many pathologies such as cancer and pre-eclampsia. Results: The aims of this study were to examine the role of this inhibitory VEGF by expressing this molecule in a model of intestinal inflammation, and to evaluate its expression as a potential new therapeutic approach for treating UC. A modified model of TNBS colitis was used to determine the effects of rVEGF164b expression on colon inflammation. Expansion of the vascular system was assessed by immunhistochemical methods and macro- and microscopic measurements of inflammation in the colon were measured. Leukocyte invasion of the tissue was measured by myeloperoxidase assay and identification and counting of lymphoid follicles. Both angio- and lymphangiogenesis were reduced by expression of rVEGF164b, which correlated with reduction in both gross and microscopic inflammatory scores. Leukocyte invasion of the tissue was also reduced by rVEGF164b expression. Conclusions: This is the first report using an endogenous inhibitory VEGF-A isoform for therapy in a model of experimental colitis. Inhibitory VEGF molecules play an important role in maintenance of gut homeostasis and may be dysregulated in UC. The results of this study suggest that restoration of rVEGF164b expression has anti-inflammatory activity in a TNBS model and warrants further examination as a possible therapeutic for UC.",
keywords = "Adenovirus, Angiogenesis, Colon, Inflammation, TNBS, Therapy, Ulcerative colitis, VEGF",
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VEGF-A isoform modulation in an preclinical TNBS model of ulcerative colitis : Protective effects of a VEGF164b therapy. / Cromer, Walter E.; Ganta, Chaitanya V.; Patel, Mihir; Traylor, James; Kevil, Christopher G.; Alexander, J. S.; Mathis, James Michael.

In: Journal of Translational Medicine, Vol. 11, No. 1, 207, 11.09.2013.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - VEGF-A isoform modulation in an preclinical TNBS model of ulcerative colitis

T2 - Protective effects of a VEGF164b therapy

AU - Cromer, Walter E.

AU - Ganta, Chaitanya V.

AU - Patel, Mihir

AU - Traylor, James

AU - Kevil, Christopher G.

AU - Alexander, J. S.

AU - Mathis, James Michael

PY - 2013/9/11

Y1 - 2013/9/11

N2 - Background: Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the USA. A key component of UC is the increase in inflammatory angiogenesis of the colon during active disease. This increase is driven to a great extent by the over expression of VEGF-A. Recently, VEGF165b (VEGF164b in mouse), an anti-angiogenic form of VEGF-A was described and its regulation was determined to be disturbed in many pathologies such as cancer and pre-eclampsia. Results: The aims of this study were to examine the role of this inhibitory VEGF by expressing this molecule in a model of intestinal inflammation, and to evaluate its expression as a potential new therapeutic approach for treating UC. A modified model of TNBS colitis was used to determine the effects of rVEGF164b expression on colon inflammation. Expansion of the vascular system was assessed by immunhistochemical methods and macro- and microscopic measurements of inflammation in the colon were measured. Leukocyte invasion of the tissue was measured by myeloperoxidase assay and identification and counting of lymphoid follicles. Both angio- and lymphangiogenesis were reduced by expression of rVEGF164b, which correlated with reduction in both gross and microscopic inflammatory scores. Leukocyte invasion of the tissue was also reduced by rVEGF164b expression. Conclusions: This is the first report using an endogenous inhibitory VEGF-A isoform for therapy in a model of experimental colitis. Inhibitory VEGF molecules play an important role in maintenance of gut homeostasis and may be dysregulated in UC. The results of this study suggest that restoration of rVEGF164b expression has anti-inflammatory activity in a TNBS model and warrants further examination as a possible therapeutic for UC.

AB - Background: Ulcerative colitis (UC) is the most common form of inflammatory bowel disease in the USA. A key component of UC is the increase in inflammatory angiogenesis of the colon during active disease. This increase is driven to a great extent by the over expression of VEGF-A. Recently, VEGF165b (VEGF164b in mouse), an anti-angiogenic form of VEGF-A was described and its regulation was determined to be disturbed in many pathologies such as cancer and pre-eclampsia. Results: The aims of this study were to examine the role of this inhibitory VEGF by expressing this molecule in a model of intestinal inflammation, and to evaluate its expression as a potential new therapeutic approach for treating UC. A modified model of TNBS colitis was used to determine the effects of rVEGF164b expression on colon inflammation. Expansion of the vascular system was assessed by immunhistochemical methods and macro- and microscopic measurements of inflammation in the colon were measured. Leukocyte invasion of the tissue was measured by myeloperoxidase assay and identification and counting of lymphoid follicles. Both angio- and lymphangiogenesis were reduced by expression of rVEGF164b, which correlated with reduction in both gross and microscopic inflammatory scores. Leukocyte invasion of the tissue was also reduced by rVEGF164b expression. Conclusions: This is the first report using an endogenous inhibitory VEGF-A isoform for therapy in a model of experimental colitis. Inhibitory VEGF molecules play an important role in maintenance of gut homeostasis and may be dysregulated in UC. The results of this study suggest that restoration of rVEGF164b expression has anti-inflammatory activity in a TNBS model and warrants further examination as a possible therapeutic for UC.

KW - Adenovirus

KW - Angiogenesis

KW - Colon

KW - Inflammation

KW - TNBS

KW - Therapy

KW - Ulcerative colitis

KW - VEGF

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U2 - 10.1186/1479-5876-11-207

DO - 10.1186/1479-5876-11-207

M3 - Article

VL - 11

JO - Journal of Translational Medicine

JF - Journal of Translational Medicine

SN - 1479-5876

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