Angiogenesis blockade as a new therapeutic approach to experimental colitis.

Angiogenesis blockade as a new therapeutic approach to experimental colitis. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

Angiogenesis blockade as a new therapeutic approach to experimental colitis. Abstract Text:

Silvio Danese,Miquel Sans,David M Spencer,Ivy Beck,Fernando ,Marian L Plunkett,Carol de la Motte,Raymond Redline,David E Shaw,Alan D Levine,Andrew P Mazar,Claudio Fiocchi,

BACKGROUND: Neoangiogenesis is a critical component of chronic inflammatory disorders. Inhibition of angiogenesis is an effective treatment in animal models of inflammation, but has not been tested in experimental colitis. AIM: To investigate the effect of ATN-161, an anti-angiogenic compound, on the course of experimental murine colitis. Method: Interleukin 10-deficient (IL10(-/-)) mice and wild-type mice were kept in ultra-barrier facilities (UBF) or conventional housing, and used for experimental conditions. Dextran sodium sulphate (DSS)-treated mice were used as a model of acute colitis. Mice were treated with ATN-161 or its scrambled peptide ATN-163. Mucosal neoangiogenesis and mean vascular density (MVD) were assessed by CD31 staining. A Disease Activity Index (DAI) was determined, and the severity of colitis was determined by a histological score. Colonic cytokine production was measured by ELISA, and lamina propria mononuclear cell proliferation by thymidine incorporation. RESULT: MVD increased in parallel with disease progression in IL10(-/-) mice kept in conventional housing, but not in IL10(-/-) mice kept in UBF. Angiogenesis also occurred in DSS-treated animals. IL10(-/-) mice with established disease treated with ATN-161, but not with ATN-163, showed a significant and progressive decrease in DAI. The histological colitis score was significantly lower in ATN-161-treated mice than in scrambled peptide-treated mice. Inhibition of angiogenesis was confirmed by a significant decrease of MVD in ATN-161-treated mice than in ATN-163-treated mice. No therapeutic effects were observed in the DSS model of colitis. ATN-161 showed no direct immunomodulatory activity in vitro. CONCLUSION: Active angiogenesis occurs in the gut of IL10(-/-) and DSS-treated colitic mice and parallels disease progression. ATN-161 effectively decreases angiogenesis as well as clinical severity and histological inflammation in IL10(-/-) mice but not in the DDS model of inflammatory bowel disease (IBD). The results provide the rational basis for considering anti-angiogenic strategies in the treatment of IBD in humans.

Angiogenesis blockade as a new therapeutic approach to experimental colitis. Publishing Authors By Initials

S Danese,M Sans,DM Spencer,I Beck,F ,ML Plunkett,C de la Motte,R Redline,DE Shaw,AD Levine,AP Mazar,C Fiocchi,

For similar peptides: oligopeptides research abstracts see: peptides: oligopeptides research

PUBMED ID PMID:

MEDLINE DATE:

Angiogenesis blockade as a new therapeutic approach to experimental colitis. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Gut

VOLUME: 56

Page Numbers: 855-62

Journal Abbreviation: Gut

ISSN: 0017-5749

DAY: 14

MONTH: 12

YEAR: 2006

Angiogenesis blockade as a new therapeutic approach to experimental colitis. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985108

Angiogenesis blockade as a new therapeutic approach to experimental colitis. Keywords Mesh Terms:

KEYWORDS: Oligopeptides

MESH TERMS: therapeutic use

Chemical & Substance for Abstract: Angiogenesis blockade as a new therapeutic approach to experimental colitis. Information

Substance Name: Dextran Sulfate

Registry Number: 9042-14-2

Grant and Affiliation Information for Angiogenesis blockade as a new therapeutic approach to experimental colitis.

AFFILIATION: Division of Gastroenterology, Istituto Clinico Humanitas, Rozzano, Milan 20089, Italy. sdanese@hotmail.com

Country: England

AGENCY: United States NIDDK

GRANT: DK50984

ACRONYM: DK

MEDLINETA: Gut

REFSOURCE:

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

Angiogenesis blockade as a new therapeutic approach to experimental colitis Related Publications

• Anaphylaxis in the emergency department: a paediatric perspective.
• Angiogenesis blockade as a new therapeutic approach to experimental colitis.
• Gastroesophageal reflux disease-associated esophagitis induces endogenous cytokine production leading to motor abnormalities.
• Immune events associated with inflammatory bowel disease.
• Immune regulation by microvascular endothelial cells: directing innate and adaptive immunity, coagulation, and inflammation.
• Inflammatory bowel disease: progress and current concepts of etiopathogenesis.
• Intestinal fibrosis in inflammatory bowel disease: progress in basic and clinical science.
• Lymphoid cells of the gastrointestinal tract. Isolation procedures.
• Mucosal T-cell immunoregulation varies in early and late inflammatory bowel disease.
• [Recognizing anaphylaxis in the emergency department]