Characterization of Rat Aortic Fragment within Collagen Gel as an Angiogenesis Model; Capillary Morphology may Reflect the Action Mechanisms of Angiogenesis Inhibitors

スポンサーリンク

概要

• 論文の詳細を見る

• A fragment of rat thoracic aorta within type I collagen gel was employed as a model of angiogenesis, including the processes of cell migration, proliferation and capillary tube formation. Endogenous angiogenic factors in this model were studied. Expressions of vascular endothelial growth factor (VEGF) and its receptor, and proteolytic enzyme activities (matrix metalloprotease-2; MMP-2 and plasminogen activator; PA) increased during angiogenesis. The angiogenesis was inhibited by VEGF receptor kinase inhibitor and MMP inhibitor, confirming that these endogenous factors played an important role in angiogenesis. Interestingly, these inhibitors induced different capillary morphologies, including differences of cell migration and sprouting. Furthermore, dexamethasone (a down-regulator of MMP and PA) and TNP-470 (an endothelial cell growth inhibitor) induced another capillary morphology. The results suggest that the capillary structure in this model is dramatically influenced by the inhibition of angiogenic signalling and extracellular matrix (ECM) degradation. We also found that a novel angiogenesis inhibitor, the microbial metabolite luminacin, which was recently identified by us (Wakabaynshi etal., J. Antiobiot., 53, 591-596 (2000)), induced a different morphology compared with other inhibitors examined, suggesting that it has a unique mechanism of action. Our results indicate that this rat aorta model should be useful for screening novel angiogenesis inhibitors.

• 公益社団法人日本薬学会の論文
• 2002-04-01

著者

• WAKABAYASHI Toshiaki

  Tsukuba Research Laboratories, Eisai Co. Ltd.

• Kawase-kageyama Rena

  Tsukuba Research Laboratories Eisai Co. Ltd.

• Hata-sugi Naoko

  Tsukuba Research Laboratories Eisai Co. Ltd.

• Wakabayashi T

  Tsukuba Research Laboratories Eisai Co. Ltd.

関連論文

• Luminacins: A Family of Capillary Tube Formation Inhibitors from Streptomyces sp. : II. Biological Activities
• Luminacins : A Family of Capillary Tube Formation Inhibitors from Streptomyces sp. : I. Taxonomy, Fermentation, Isolation, Physico-chemical Properties and Structure Elucidation
• Borrelidin is an Angiogenesis Inhibitor; Disruption of Angiogenic Capillary Vessels in a Rat Aorta Matrix Culture Modle
• Characterization of Rat Aortic Fragment within Collagen Gel as an Angiogenesis Model; Capillary Morphology may Reflect the Action Mechanisms of Angiogenesis Inhibitors

スポンサーリンク