Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P39060 (endostatin)
 2,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tears in the peripheral part of the menisci have a better healing potential than tears in the central part, because the central two-thirds of the menisci are avascular. The avascular status of the meniscus is maintained by the expression of antiangiogenic factors such as endostatin. The distribution of endostatin in the menisci correlates with the degree of vascularization. Endostatin immunostaining is strong in the avascular zone and reduced in the vascularized outer one-third. Endostatin interacts with signal transduction of the vascular endothelial growth factor (VEGF) by reducing VEGF-induced kinase (Erk1/2) phosphorylation. VEGF plays an important role in angiogenesis in fetal menisci and it is down-regulated in the adult meniscus. We hypothesized that healing of meniscal tears in the avascular zone can be promoted by the local application of the angiogenic factor VEGF. To evaluate this hypothesis a tear was created in the avascular zone of the medial meniscus in 18 merino sheep. The tear was then repaired with an uncoated suture (group 1), a suture coated with PDLLA (group 2), and by a suture coated with PDLLA/VEGF (group 3). After 6 weeks we observed increased factor VIII immunostaining in the VEGF-treated group. However, in this treatment group (VEGF/PDLLA) no meniscus healed. In the uncoated suture group and in the PDLLA-coated suture group partial healing was observed in three animals and complete healing in three animals, respectively. Factor VIII expression is normally restricted to vascular endothelial cells. In this study, however, single endothelial cells could be detected in the menisci of the VEGF/PDLLA group. This finding suggests that the application of VEGF might have stimulated proliferation of vascular endothelial cells but the application of VEGF was not successful in stimulating the more complex process of vasculogenesis. Further immunohistochemical examinations of the specimen have shown that in the VEGF/PDLLA group there is strong immunostaining against matrix metalloproteinase 13 (MMP-13). In vitro studies have shown that VEGF can stimulate chondrocytes to proliferate but also to express MMP-13 via HIF1-alpha induction. Since meniscal fibrochondrocytes express the VEGF receptor 2 (KDR) the induction of MMP expression might be another factor which inhibits healing despite increased angiogenesis. In conclusion, the local application of VEGF via PDLLA-coated sutures does not promote meniscal healing. A single growth factor might not always be a promising tool for the promotion of tissue repair. Further studies have to find out if growth factor combinations (VEGF and angiopoitin) might be more effective in stimulating vasculogenesis during meniscal healing.
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PMID:Locally applied angiogenic factors--a new therapeutic tool for meniscal repair. 1632 Aug 30

The formation of new blood vessels permits a supply of nutrients and oxygen to the proliferating synovial cells and augmented inflammatory cell mass in rheumatoid arthritis (RA). Angiogenesis inhibition is not dependent on a down-regulated immune system. Therefore, angiogenesis is an attractive target in treating rheumatoid arthritis. To confirm the effect of recombinant human endostatin, an angiogenesis inhibitor, on inflammatory angiogenesis and to elucidate the related mechanisms, rat adjuvant arthritis model induced by Freund's complete adjuvant was used. The secondary arthritis was evaluated by using clinical scores and determining the volume of hind paw swelling. The number of new blood vessels was counted under microscope based on HE (hematoxylin and eosin) staining and positive immunoreactivity of factor VIII related antigen. factor VIII related antigen and vascular endothelial growth factor (VEGF) expressions in synovial tissue were determined by using immunohistochemistry. It was found that endostatin attenuated rat secondary paw swelling induced by Freund's complete adjuvant in a dose-dependent manner. Meanwhile, the number of new blood vessels in synovial tissue stained with HE was reduced after treatment with endostatin, which was proved by the positive immunostaining of factor VIII related antigen. Further, endostatin decreased the expression of VEGF in both cartilage and synovial tissue. These suggest that endostatin inhibiting VEGF expression contributes to the regression of rat adjuvant arthritis.
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PMID:Blockage of the formation of new blood vessels by recombinant human endostatin contributes to the regression of rat adjuvant arthritis. 1749 Jun 37