MATRIXINS AND THEIR INHIBITORS IN ANGIOGENESIS

血管生成是新生血管形成的基本过程 阵 它对发育、生殖和创伤至关重要 治愈 不受控制的新血管形成在癌症中起作用， 类风湿、血管和其他疾病。 血管生成对于 为肿瘤生长提供氧气和营养， 是癌细胞转移的通道 血管生成抑制剂可能成为 一种最有前途的饥饿肿瘤细胞的药物， 防止癌细胞扩散。 血管生成涉及细胞外基质的蛋白水解消化 血管内皮细胞下面的蛋白质如胶原 层次。 这项研究的长期目标是阐明 新血管形成的机制，以确定 胶原降解基质蛋白（基质金属蛋白酶，MMPs） 包括膜型I基质金属蛋白酶，MMPs），包括 胶原酶/明胶酶（MMP-2、MMP-9）和间质胶原酶 （MMP-1）在血管生成中的作用。 将检验以下两个假设。 首先，在血管生成条件下，例如在存在血管内皮细胞的情况下， 内皮生长因子和/或碱性成纤维细胞生长因子， 内皮细胞将产生胶原降解基质蛋白， I型和IV型胶原蛋白 每种胶原蛋白降解的作用 基质蛋白在人微血管内皮细胞介导的胶原中的作用 溶解将被解剖与高度选择性，有效的，和新颖的 基质蛋白的合成抑制剂。 第二，胶原降解基质素 是血管生成所必需的，它们可以调节内皮细胞 增殖、迁移和管形成。 每个人的作用 胶原降解基质蛋白在体外血管生成的每个步骤中将 通过合成基质蛋白抑制剂的干预进行评估。

DESCRIPTION: Angiogenesis is a fundamental process of new blood vessel formation. It is critical for development, reproduction, and wound healing. Uncontrolled neovascularization plays a role in cancer, rheumatoid, vascular and other diseases. Angiogenesis is essential for providing oxygen and nutrients for tumor growth and for generating a gateway for cancer cell metastasis. Angiogenesis inhibitors may become one of the most promising types of drugs for starving tumor cells and preventing the spread of cancer cells. Angiogenesis involves proteolytic digestion of the extracellular matrix proteins such as collagens underlying the blood vessel endothelial cell layers. The long term goals of this research are to elucidate the mechanisms by which new blood vessels are formed, to identify the role of collagen-degrading matrixins (matrix metalloproteinases, MMPs) including membrane-type I matrix metalloproteinases, MMPs) including collagenases/gelatinases (MMP-2, MMP-9), and interstitial collagenase (MMP-1), in angiogenesis. The following two hypotheses will be tested. First, under angiogenic conditions, such as in the presence of vascular endothelial growth factor and/or basic fibroblast growth factor, endothelial cells will produce collagen degrading matrixins to break down type I and IV collagens. The role of each collagen-degrading matrixin in human microvascular endothelial cell -mediated collagen dissolution will be dissected with highly selective, potent, and novel synthetic inhibitors of matrixins. Second, collagen-degrading matrixins are required for angiogenesis and they may regulate endothelial cell proliferation, migration, and tube formation. The role of each collagen-degrading matrixin in each step of angiogenesis in vitro will be assessed through intervention by the synthetic matrixin inhibitors.