Characterization of rat aortic fragment within collagen gel as an angiogenesis model; capillary morphology may reflect the action mechanisms of angiogenesis inhibitors.
Characterization of rat aortic fragment within collagen gel as an angiogenesis model; capillary morphology may reflect the action mechanisms of angiogenesis inhibitors.
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胶原凝胶内大鼠主动脉碎片作为血管生成模型的表征；
DOI：
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发表时间：
2002
影响因子：
2
通讯作者：
T. Wakabayashi
中科院分区：
文献类型：
--
作者：
N. Hata;Rena Kawase;T. Wakabayashi
采用 I 型胶原凝胶内的大鼠胸主动脉片段作为血管生成模型，包括细胞迁移、增殖和毛细管形成的过程。研究了该模型中的内源性血管生成因子。血管生成过程中血管内皮生长因子（VEGF）及其受体的表达以及蛋白水解酶活性（基质金属蛋白酶-2；MMP-2和纤溶酶原激活剂；PA）增加。 VEGF受体激酶抑制剂和MMP抑制剂抑制血管生成，证实这些内源因子在血管生成中发挥重要作用。有趣的是，这些抑制剂诱导了不同的毛细血管形态，包括细胞迁移和发芽的差异。此外，地塞米松（MMP 和 PA 的下调剂）和 TNP-470（内皮细胞生长抑制剂）诱导另一种毛细血管形态。结果表明，该模型中的毛细血管结构受到血管生成信号传导和细胞外基质（ECM）降解的抑制的显着影响。我们还发现，我们最近发现的一种新型血管生成抑制剂，即微生物代谢物鲁米那星（Wakabayashi et al., J. Antiobiot., 53, 591-596 (2000)），与其他检查的抑制剂相比，诱导了不同的形态，表明它具有独特的作用机制。我们的结果表明，这种大鼠主动脉模型应该可用于筛选新型血管生成抑制剂。
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 (Wakabayashi et al., 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.
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DOI：
10.1073/pnas.94.25.13612
发表时间：
1997-12-09
影响因子：
11.1
作者：
Senger, DR;Claffey, KP;Detmar, M
通讯作者：
Detmar, M
DOI：
--
发表时间：
1994-11
期刊：
The American journal of pathology
影响因子：
--
作者：
R. Nicosia;S. Nicosia;M. Smith
通讯作者：
R. Nicosia;S. Nicosia;M. Smith
大鼠主动脉损伤后释放的内源性碱性成纤维细胞生长因子的血管生成作用。
DOI：
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发表时间：
1993
期刊：
The American journal of pathology
影响因子：
--
作者：
Villaschi,S;Nicosia,RF
通讯作者：
Nicosia,RF
地塞米松选择性调节基础和脂多糖诱导的金属蛋白酶以及人肺泡巨噬细胞产生金属蛋白酶的组织抑制剂。
DOI：
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发表时间：
1991
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Shapiro,SD;Campbell,EJ;Kobayashi,DK;Welgus,HG
通讯作者：
Welgus,HG
影响因子：
3.3
作者：
KLEIN, S;GIANCOTTI, FG;RIFKIN, DB
通讯作者：
RIFKIN, DB