Inappropriate Angiogenic Response as a Novel Mechanism of Duodenal Ulceration and Impaired Healing
| Autor: | Tetyana Khomenko, Sandor Szabo, Klara Osapay, Judah Folkman, Ximing Xiong, Joseph Shiloach, Zsuzsanna Sandor, Ganna Tolstanova, Xiaoming Deng, Longchuan Chen |
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| Rok vydání: | 2011 |
| Předmět: |
Vascular Endothelial Growth Factor A
medicine.medical_specialty Pathology Physiology Cysteamine Matrix Metalloproteinase Inhibitors Gastroenterology Article Rats Sprague-Dawley Pathogenesis Duodenal ulceration Internal medicine Nitriles medicine Animals Enzyme Inhibitors Intestinal Mucosa Angiostatins Tissue Inhibitor of Metalloproteinase-2 Wound Healing Tissue Inhibitor of Metalloproteinase-1 Neovascularization Pathologic Mechanism (biology) business.industry Hepatology digestive system diseases Endostatins Rats Duodenal ulcer Disease Models Animal Matrix Metalloproteinase 9 Duodenal Ulcer Etiology Matrix Metalloproteinase 2 Female Gastrointestinal ulcer business Delayed healing |
| Zdroj: | Dig Dis Sci |
| ISSN: | 1573-2568 0163-2116 |
| DOI: | 10.1007/s10620-011-1753-4 |
| Popis: | 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. 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. 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. 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. 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. |
| Databáze: | OpenAIRE |
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