Mouse Arteries Predisposed to Neointimal Formation

小鼠动脉易于形成新内膜

基本信息

  • 批准号:
    7171564
  • 负责人:
  • 金额:
    $ 37.75万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2006
  • 资助国家:
    美国
  • 起止时间:
    2006-02-01 至 2010-01-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): This proposal will examine how the sphingosine 1-phosphate (S1P) regulates smooth muscle cell migration. Our preliminary data show that SMCs of FVB mice migrate well in response to S1P and that migration is inhibited in the presence of a sphingosine kinase inhibitor (SphK). In total contrast, cells of C57BL/6 mice are not stimulated by S1P and the SphK inhibitor actually stimulates migration. We believe these differences are due to S1P receptor expression. FVB express S1P1 and S1P3 but little S1P2. In contrast C57BL/6 cells strongly express S1P2with reduced levels of S1P1 and S1P3. The first aim will measure circulating S1P levels in arteries of FVB and C57BL76 mice before and at times after injury. The activities of the S1 P-kinase and S1 P-phosphatase and expression of kinases, phosphatase and lyase will also be determined by PCR. S1P will also be determined in lipoprotein and in lipoprotein depleted fractions of plasma. We will also determine if plasma S1P can stimulate events in arteries and importantly affect SMC migration. The second aim will determine if loss of SphK activity influences SMC migration in injured mice arteries. These studies will use SphK null mice as well as a new inhibitor to block SphK activity. The third aim will determine the importance of specific S1P receptors for SMC to migrate. Experiments will be carried out using siRNA to S1P1, S1P2 and S1P3, and S1P2 and S1P3 null cells. The arteries of these mice will be subjected to injury and SMC migration and neointimal development measured. The final aim will determine how S1P signals and so regulates migration. These studies will ask if S1P signals via EGF receptor and if different S1P act differently. We will also determine if PKB and Rac are necessary for SMC migration and if blockade to the EGF receptor will prevent SMC migration and neointimal development in injured arteries.
描述(由申请人提供):本提案将研究1-磷酸鞘氨醇(S1 P)如何调节平滑肌细胞迁移。我们的初步数据表明,平滑肌细胞的FVB小鼠迁移以及响应S1 P和迁移抑制鞘氨醇激酶抑制剂(SphK)的存在下。相反,C57 BL/6小鼠的细胞不受S1 P刺激,SphK抑制剂实际上刺激迁移。我们认为这些差异是由于S1 P受体的表达。FVB表达S1 P1和S1 P3,但S1 P2很少。相反,C57 BL/6细胞强烈表达S1 P2,而S1 P1和S1 P3的水平降低。第一个目的是测量FVB和C57 BL 76小鼠在损伤之前和之后的动脉中的循环S1 P水平。还将通过PCR测定SlP-激酶和SlP-磷酸酶的活性以及激酶、磷酸酶和裂解酶的表达。还将测定血浆中脂蛋白和脂蛋白耗竭组分中的S1 P。我们还将确定血浆S1 P是否可以刺激动脉中的事件并重要地影响SMC迁移。第二个目标是确定SphK活性的丧失是否会影响受损小鼠动脉中SMC的迁移。这些研究将使用SphK null小鼠以及一种新的抑制剂来阻断SphK活性。第三个目标将确定特定S1 P受体对SMC迁移的重要性。将使用针对S1 P1、S1 P2和S1 P3以及S1 P2和S1 P3缺失细胞的siRNA进行实验。这些小鼠的动脉将受到损伤,并测量SMC迁移和新生内膜发育。最终的目标将确定S1 P如何发出信号,从而调节迁移。这些研究将询问S1 P是否通过EGF受体发出信号,以及不同的S1 P是否有不同的作用。我们还将确定PKB和Rac是否是SMC迁移所必需的,以及阻断EGF受体是否会阻止SMC迁移和损伤动脉中的新生内膜发育。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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MICHAEL A. REIDY其他文献

MICHAEL A. REIDY的其他文献

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{{ truncateString('MICHAEL A. REIDY', 18)}}的其他基金

Mouse Arteries Predisposed to Neointimal Formation
小鼠动脉易于形成新内膜
  • 批准号:
    7576825
  • 财政年份:
    2006
  • 资助金额:
    $ 37.75万
  • 项目类别:
Mouse Arteries Predisposed to Neointimal Formation
小鼠动脉易于形成新内膜
  • 批准号:
    7365229
  • 财政年份:
    2006
  • 资助金额:
    $ 37.75万
  • 项目类别:
Mouse Arteries Predisposed to Neointimal Formation
小鼠动脉易于形成新内膜
  • 批准号:
    7050713
  • 财政年份:
    2006
  • 资助金额:
    $ 37.75万
  • 项目类别:
The Role of Proteinases and Vascular Lesion Formation
蛋白酶和血管病变形成的作用
  • 批准号:
    6889573
  • 财政年份:
    2003
  • 资助金额:
    $ 37.75万
  • 项目类别:
The Role of Proteinases and Vascular Lesion Formation
蛋白酶和血管病变形成的作用
  • 批准号:
    6611772
  • 财政年份:
    2003
  • 资助金额:
    $ 37.75万
  • 项目类别:
The Role of Proteinases and Vascular Lesion Formation
蛋白酶和血管病变形成的作用
  • 批准号:
    7028908
  • 财政年份:
    2003
  • 资助金额:
    $ 37.75万
  • 项目类别:
The Role of Proteinases and Vascular Lesion Formation
蛋白酶和血管病变形成的作用
  • 批准号:
    6725352
  • 财政年份:
    2003
  • 资助金额:
    $ 37.75万
  • 项目类别:
ILK SIGNAL & CYCLIN DL EXPRESSION POST ARTERIAL INJURY
伊尔克信号
  • 批准号:
    6459082
  • 财政年份:
    2002
  • 资助金额:
    $ 37.75万
  • 项目类别:
ILK SIGNAL & CYCLIN DL EXPRESSION POST ARTERIAL INJURY
伊尔克信号
  • 批准号:
    6622901
  • 财政年份:
    2002
  • 资助金额:
    $ 37.75万
  • 项目类别:
ILK SIGNAL & CYCLIN DL EXPRESSION POST ARTERIAL INJURY
伊尔克信号
  • 批准号:
    6726082
  • 财政年份:
    2002
  • 资助金额:
    $ 37.75万
  • 项目类别:

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