Regulation of angiogenesis by lysophospholipids

溶血磷脂对血管生成的调节

• 批准号: 6893130
• 负责人: CAROL M RIVERA-LOPEZ
• 金额: $ 3.78万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-02 至 2008-01-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6893130
• 关键词: angiogenesis; angiogenesis factor; antineoplastics; athymic mouse; bioassay; biological signal transduction; cell growth regulation; cell migration; cell surface receptors; chick embryo; drug design /synthesis /production; enzyme activity; human tissue; laboratory mouse; lysolecithins; lysophospholipids; phosphorylation; predoctoral investigator; receptor binding; receptor expression; sphingosine; vascular endothelial growth factors; vascular endothelium

DESCRIPTION (provided by applicant): The purpose of this research project is to determine the roles of lysophospholipids in the regulation of angiogenesis. The function of S1P is pretty well understood, however there are some issues that are unclear. LPA involvement is currently in debate due to the ambiguity of the data that have been published. Both of these molecules act through activation of G-protein coupled receptors of the Endothelial Differentiation Gene (EDG) family. Some studies have demonstrated EDG-1 receptor to be involved in the regulation of angiogenesis, however, the function of other EDG receptors have not been completely elucidated. The goal of this proposal is to determine and understand the roles of S1P and LPA in the regulation of angiogenesis by studying activation and inhibition of their receptors using a library of selective compounds. First, in vitro models of angiogenesis (migration and proliferation assays) in Human Microvascular Endothelial Cells will be performed and then, in vivo assays in mice will be used to confirm in vitro data. With this information it would be easier to design selective pharmaceutical agents for the treatment of conditions, such as cancer, in which angiogenesis is involved.

描述（由申请人提供）：该研究项目的目的是确定溶物磷脂在血管生成调节中的作用。 S1P的功能非常了解，但是有些问题尚不清楚。由于已发布的数据的模棱两可，LPA参与目前正在争论。这两个分子都通过激活内皮分化基因（EDG）家族的G蛋白偶联受体的激活作用。一些研究表明，EDG-1受体与血管生成有关，但是，其他EDG受体的功能尚未完全阐明。该提案的目的是使用选择性化合物库来确定和理解S1P和LPA在调节血管生成中的作用。首先，将进行人类微血管内皮细胞中血管生成的体外模型（迁移和增殖测定），然后将使用小鼠的体内分析来确认体外数据。有了这些信息，设计有选择性的药物以治疗涉及血管生成的疾病（例如癌症）会更容易。