BASIC FIBROBLAST GROWTH FACTOR AND MYOCARDIAL ANGIOGENESIS

碱性成纤维细胞生长因子和心肌血管生成

基本信息

项目摘要

Several polypeptide growth factors have been identified with the ability to induce blood vessel development (angiogenesis), and the overall project goal is to utilize such growth factors to facilitate coronary collateral development in patients with ischemic heart disease. We have shown that basic fibroblast growth factor (bFGF) and vascular endothelial growth factor, both angiogenic polypeptide growth factors, enhance coronary collateral development in dogs when administered repeatedly into the coronary circulation, or, in the case of bFGF, when administered daily into the systemic arterial circulation for seven days. These routes of administration, although acceptable in experimental animals, are not practical in human subjects. Most recently, we have shown that two single doses of bFGF administered into the left main coronary artery enhance coronary collateral flow in dogs, a regimen that would be feasible in human subjects. Dogs were subjected to gradual occlusion of the left circumflex coronary artery and randomized to receive bFGF 100 micrograms/kg or a vehicle control as an intracoronary bolus on one or two occasions (2 days between doses). Collateral perfusion was assessed during maximal coronary vasodilatation 17 days after treatment. Maximal collateral flow in dogs that received two doses of bFGF exceeded that of control dogs by 39% (P<0.0005). Based on these and a number of earlier investigations, we have obtained an IND (Investigational New Drug) for a Phase I study in human subjects. This is a randomized, double-blind safety study with a typical dose escalation format in which bFGF (or vehicle) is administered into the coronary circulation. The first patients entered into the study in July, 1995. Additional preclinical studies are underway to assess the potential of gene therapy to effect coronary angiogenesis. Gene therapy represents an attractive alternative to the administration of polypeptide growth factors. Sustained local expression of angiogenic gene products could result in site-specific angiogenic stimulation following a single intracoronary treatment.
几种多肽生长因子已被确定具有这种能力

项目成果

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E UNGER其他文献

E UNGER的其他文献

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{{ truncateString('E UNGER', 18)}}的其他基金

A MODEL OF ARTERIAL SMOOTH MUSCLE CELL PROLIFERATION TO STUDY RESTENOSIS
用于研究再狭窄的动脉平滑肌细胞增殖模型
  • 批准号:
    3843381
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
PROMOTION OF MYOCARDIAL ANGIOGENESIS USING PEPTIDE GROWTH FACTORS
利用肽生长因子促进心肌血管生成
  • 批准号:
    3843382
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
A MODEL OF ARTERIAL SMOOTH MUSCLE CELL PROLIFERATION TO STUDY RESTENOSIS
用于研究再狭窄的动脉平滑肌细胞增殖模型
  • 批准号:
    3858120
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
PROMOTION OF MYOCARDIAL ANGIOGENESIS USING PEPTIDE GROWTH FACTORS
利用肽生长因子促进心肌血管生成
  • 批准号:
    3779616
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:
PROMOTION OF MYOCARDIAL ANGIOGENESIS VIA DIRECT APPLICATION OF FGF TO HEART
通过直接将 FGF 应用于心脏促进心肌血管生成
  • 批准号:
    3858121
  • 财政年份:
  • 资助金额:
    --
  • 项目类别:

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