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Inappropriate angiogenic response as a novel mechanism of duodenal ulceration and impaired healing.
- Source :
-
Digestive diseases and sciences [Dig Dis Sci] 2011 Oct; Vol. 56 (10), pp. 2792-801. Date of Electronic Publication: 2011 Jul 07. - Publication Year :
- 2011
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Abstract
- Background: Despite recent advances and better understanding of the etiology and the pathogenesis of gastrointestinal ulcer diseases, e.g., duodenal ulcer, the molecular events leading to ulcer development, delayed healing, and recurrence remain poorly elucidated.<br />Aims: After we found that duodenal ulcers did not heal despite increased levels of vascular endothelial growth factor (VEGF), we tested the hypothesis that an imbalance in angiogenic VEGF and anti-angiogenic endostatin and angiostatin might be important in the development and delayed healing of experimental duodenal ulcers.<br />Methods: Levels of VEGF, endostatin, and angiostatin, and the expression and activity of related matrix metalloproteinases (MMP) 2 and 9 were measured in scrapings of rat proximal duodenal mucosa in the early and late stages of chemically induced duodenal ulceration. Furthermore, animals were treated with recombinant endostatin and MMP 2 inhibitor to test the relationship between MMP2 and endostatin and their involvement in healing of experimental duodenal ulcers.<br />Results: A concurrent increase of duodenal VEGF, endostatin, and angiostatin was noted during duodenal ulceration. Endostatin treatment aggravated duodenal ulcer. Levels of MMP2, but not MMP9, were increased. Inhibition of MMP2 reduced levels of endostatin and angiostatin, and attenuated duodenal ulcers.<br />Conclusions: Increased levels of endostatin and angiostatin induced by MMP2 delayed healing of duodenal ulcers despite concurrently increased VEGF. Thus, an inappropriate angiogenic response or "angiogenic imbalance" may be an important new mechanism in ulcer development and impaired healing.
- Subjects :
- Animals
Cysteamine adverse effects
Disease Models, Animal
Duodenal Ulcer chemically induced
Duodenal Ulcer physiopathology
Enzyme Inhibitors pharmacology
Female
Intestinal Mucosa metabolism
Intestinal Mucosa pathology
Intestinal Mucosa physiopathology
Matrix Metalloproteinase 2 drug effects
Matrix Metalloproteinase 2 metabolism
Matrix Metalloproteinase 9 metabolism
Matrix Metalloproteinase Inhibitors
Neovascularization, Pathologic physiopathology
Nitriles adverse effects
Rats
Rats, Sprague-Dawley
Tissue Inhibitor of Metalloproteinase-1 metabolism
Tissue Inhibitor of Metalloproteinase-2 metabolism
Angiostatins metabolism
Duodenal Ulcer metabolism
Endostatins metabolism
Neovascularization, Pathologic metabolism
Vascular Endothelial Growth Factor A metabolism
Wound Healing physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1573-2568
- Volume :
- 56
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Digestive diseases and sciences
- Publication Type :
- Academic Journal
- Accession number :
- 21735086
- Full Text :
- https://doi.org/10.1007/s10620-011-1753-4