PREVENTION OF VEIN GRAFT SPASM

预防移植静脉痉挛

基本信息

  • 批准号:
    6884077
  • 负责人:
  • 金额:
    $ 49.36万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2003
  • 资助国家:
    美国
  • 起止时间:
    2003-04-01 至 2007-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Vasospasm occurs in the blood vessels used for vascular bypass operations. This spasm is due to impaired relaxation of the smooth muscle. Relaxation is mediated by cyclic nucleotide-dependent signaling pathways. We have demonstrated that the phosphorylation of a small heat shock protein, HSP20 represents a point in which the cyclic nucleotide signaling pathways converge to cause relaxation. The hypotheses of this investigation are that vasorelaxing molecules, engineered to include HSP20 motifs and protein transduction domains, will prevent 1) short term vein graft failure due to vasospasm and 2) long term graft failure by better preservation of the graft during harvest and by the prevention of intimal hyperplasia. The specific aims of this investigation are: #1: Generate recombinant HSP20 linked to a protein transduction domain (PTD) and determine if this engineered protein reverses human vascular smooth muscle spasm ex vivo. #2: Determine the effect of PTD-HSP20 on dynamic cytoskeletal processes relevant to intimal hyperplasia. #3: Determine the feasibility of protein transduction of HSP20 analogues of vein grafts in vivo. The goal of this project is to engineer biomolecules that enhance vein graft preservation by directly introducing the analogues of an endogenous relaxing protein (HSP20) into the smooth muscle. Vein grafts represent an ideal target for these therapeutic approaches in that the graft can be treated ex vivo, thus providing an optimal environment for the localization of engineered protein/peptide therapeutics. This represents a novel approach in that the receptors and signaling cascades are "bypassed" and the effector protein/peptide is directly introduced into the target cell. This represents a "post-genomic" platform for engineering biologically active protein/peptide molecules.
描述(由申请人提供):

项目成果

期刊论文数量(0)
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Colleen M Brophy其他文献

Colleen M Brophy的其他文献

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{{ truncateString('Colleen M Brophy', 18)}}的其他基金

Cell permeant peptidomimetics to prevent delayed vasospasm and neurological deficits after subarachnoid hemorrhage
细胞渗透性肽模拟物可预防蛛网膜下腔出血后迟发性血管痉挛和神经功能缺损
  • 批准号:
    10384341
  • 财政年份:
    2022
  • 资助金额:
    $ 49.36万
  • 项目类别:
PRESERVATION OF ENDOTHELIAL DEPENDENT RELAXATION
保护内皮依赖性舒张
  • 批准号:
    8803361
  • 财政年份:
    2013
  • 资助金额:
    $ 49.36万
  • 项目类别:
PRESERVATION OF ENDOTHELIAL DEPENDENT RELAXATION
保护内皮依赖性舒张
  • 批准号:
    8971994
  • 财政年份:
    2013
  • 资助金额:
    $ 49.36万
  • 项目类别:
PRESERVATION OF ENDOTHELIAL DEPENDENT RELAXATION
保护内皮依赖性舒张
  • 批准号:
    8442056
  • 财政年份:
    2013
  • 资助金额:
    $ 49.36万
  • 项目类别:
Prevention of Vein Graft Failure
预防静脉移植失败
  • 批准号:
    7822281
  • 财政年份:
    2009
  • 资助金额:
    $ 49.36万
  • 项目类别:
Prevention of Vein Graft Failure
预防静脉移植失败
  • 批准号:
    7799153
  • 财政年份:
    2003
  • 资助金额:
    $ 49.36万
  • 项目类别:
Prevention of Vein Graft Failure
预防静脉移植失败
  • 批准号:
    9188770
  • 财政年份:
    2003
  • 资助金额:
    $ 49.36万
  • 项目类别:
Prevention of Vein Graft Failure
预防静脉移植失败
  • 批准号:
    7371243
  • 财政年份:
    2003
  • 资助金额:
    $ 49.36万
  • 项目类别:
Prevention of Vein Graft Failure
预防静脉移植失败
  • 批准号:
    8039215
  • 财政年份:
    2003
  • 资助金额:
    $ 49.36万
  • 项目类别:
Prevention of Vein Graft Failure
预防静脉移植失败
  • 批准号:
    8974847
  • 财政年份:
    2003
  • 资助金额:
    $ 49.36万
  • 项目类别:

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  • 批准号:
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  • 财政年份:
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