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
• 负责人: E UNGER
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3843382
• 关键词: angiogenesis; collateral circulation; coronary disorder; dogs; fibroblast growth factor; heart circulation; heart disorder; heart pharmacology; myocardial ischemia /hypoxia; vascular smooth muscle

Several polypeptides with the potential to cause blood vessel growth (angiogenesis) have been sequenced and synthesized during the last few years. Our ultimate goal is to utilize these angiogenic agent(s) to facilitate myocardial revascularization in patients with coronary heart disease. Basic fibroblast growth factor (bFGF) is a potent angiogenic peptide that may play an important role in coronary collateral formation. We previously found that intracoronary administration of bFGF increases collateral blood flow (CBF) in vivo, in a canine model of myocardial ischemia. In this study, we examined the effect of systemic bFGF on CBF in the same model, and assessed its potential side effects. Progressive constriction of the LCX coronary artery was induced of 20 dogs by placing ameroid constrictors on the vessel. Beginning on day 10, dogs received daily injection of bFGF (1.74 mg, n=10) or saline (n=10) into the left atrium. Treatment was maintained for 28 days. Microsphere blood flow was determined during maximal vasodilation on a weekly basis, beginning on day 3. CBF was expressed as an ischemic/normal zone (IZ/NZ) ratio. No adverse systemic effects were apparent. During the first week of treatment, the IZ/NZ ratio improved from 0.06 to 0.34 in bFGF treated dogs, while improving from 0.12 to 0.16 in controls (p=0.015, bFGF vs. control). During the second week, the IZ/NZ ratio increased from 0.34 to 0.42 in bFGF treated dogs, and from 0.16 to 0.19 in controls (p<0.001, bFGF vs. control). The disparity between groups, however, diminished during the third and fourth weeks of treatment. The acceleration of collateral formation was similar to that observed previously with intracoronary administration. The "catch up" phenomenon observed during weeks 3 and 4 suggests that there is a ceiling for the bFGF response, or, more likely, the observed increase in CBF abolishes ischemia in this canine model of single vessel coronary occlusion, thereby removing any further stimulus to collateral development.

几种可能导致血管生长的多肽 在过去的几年里， 年 我们的最终目标是利用这些血管生成剂， 促进冠心病患者心肌血运重建 疾病 碱性成纤维细胞生长因子（bFGF）是一种有效的血管生成因子， 肽，可能在冠状动脉侧支形成中发挥重要作用。 我们以前发现，冠状动脉内给予bFGF 在犬心肌缺血模型中， 缺血 在这项研究中，我们研究了全身bFGF对CBF的影响， 并评估其潜在的副作用。 进步 20只狗，用颈动脉结扎法造成LCX冠状动脉狭窄， 血管上的ameroid收缩器。 从第10天开始，犬接受 每日左侧皮下注射bFGF（1.74mg，n=10）或生理盐水（n=10 中庭 治疗持续28天。 微球血流 从第1天开始，每周在最大血管舒张期间测定 3. CBF表示为缺血/正常区（IZ/NZ）比率。 没有 对全身有明显的不良影响。 第一周 bFGF处理组IZ/NZ比值由0.06提高到0.34 犬，而对照组从0.12改善至0.16（p=0.015，bFGF vs. 对照）。 在第二周期间，IZ/NZ比率从0.34增加到0.34。 0.42在bFGF处理的狗中为0.16 - 0.19（p<0.001， bFGF对比对照）。 然而，群体之间的差距缩小了 在治疗的第三和第四周。 的加快 侧支形成与先前观察到的相似， 冠状动脉内给药。 观察到的“追赶”现象， 第3周和第4周表明bFGF反应有一个上限，或者， 更有可能的是，观察到的CBF增加消除了缺血， 单血管冠状动脉闭塞的犬模型，从而去除任何 进一步刺激抵押品的发展。