STIMULATION OF HUMAN CORONARY ANGIOGENESIS WITH BASIC FGF

用碱性 FGF 刺激人冠状动脉血管生成

• 批准号: 6332560
• 负责人: Michael Simons
• 金额: $ 11.25万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-15 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6332560
• 关键词: angiogenesis; cardiovascular disorder chemotherapy; cardiovascular disorder diagnosis; clinical research; coronary vessels; drug delivery systems; fibroblast growth factor; human subject; miniature swine; myocardial ischemia /hypoxia; noninvasive diagnosis; nuclear magnetic resonance spectroscopy; protein tyrosine kinase; receptor binding

The purpose of the present study is to the clinical efficacy of basic fibroblast growth factors (bFGF) in coronary angiogenesis in the setting of chronic myocardial ischemia. Ischemic coronary disease is the leading cause of morbidity and mortality in the Western world. Most available therapeutic approaches aim either at relieving symptoms by reducing myocardial oxygen demand, preventing further disease progression by modifying risk factors, restoring flow to a localized segment of the arterial tree (angioplasty) or bypassing obstruction (bypass surgery). However, no attempts have been made to restore blood supply to the myocardium by providing new venues for blood flow. Therapeutic angiogenesis may serve this goal. Angiogenesis is a complex process involving endothelial and smooth muscle cell proliferation and migration, formation of new capillaries, breakdown of existing extracellular matrix and formation of a new one. Relatively little is know regarding physiological importance and therapeutic potential of this process in chronic myocardial ischemia and molecular cellular events involved in its regulation are poorly understood. Preliminary investigation using animal models have shown that bFGF can be used to stimulate physiologically significant angiogenesis in myocardial ischemia. However, to date there has been no experience with the use of this growth factor in patients. The present study, therefore, will examine 3 Specific Aims: I. Angiogenic efficiency of bFGF chronic myocardial ischemia; II. Role of magnetic resonance imaging in noninvasive assessment of coronary angiogenesis; III. valuation of other tyrosine kinase ligands in stimulation of angiogenesis in chronic myocardial ischemia.

本研究的目的是为了临床疗效的基本 成纤维细胞生长因子（bFGF）在冠状动脉血管生成中的作用 慢性心肌缺血缺血性冠状动脉疾病 是西方世界发病率和死亡率的主要原因。大多数可用 治疗方法的目的是通过减少 心肌需氧量，防止疾病进一步进展， 修改风险因素，恢复血流到局部部分， 动脉树（血管成形术）或旁路阻塞（旁路手术）。 然而，没有尝试恢复血液供应， 通过为血液流动提供新的场所。治疗 血管生成可以达到这个目的。血管生成是一个复杂的过程 涉及内皮和平滑肌细胞增殖和迁移， 形成新的毛细血管，分解现有的细胞外基质 并形成一个新的。关于这一点我们知之甚少 这一过程的生理重要性和治疗潜力， 慢性心肌缺血及其相关的分子细胞事件 规则理解得很少。使用动物进行初步调查 模型显示bFGF可用于生理刺激， 在心肌缺血中显著的血管生成。然而，到目前为止， 没有在患者中使用这种生长因子的经验。的 因此，本研究将探讨3个具体目标：I.血管生成 bFGF对慢性心肌缺血的疗效; II.磁性的作用 共振成像在冠状动脉血管生成的非侵入性评估中的应用; III. 其它酪氨酸激酶配体在刺激血管生成中的价值 慢性心肌缺血