DETERMINANTS OF CORONARY COLLATERAL DEVELOPMENT

描述：缺血心脏的存活依赖于生长 侧支循环。然而，抵押品开发是 往往不足以完全满足老年人的血液供应需求 受损的心肌。这个研究团队的目标之一是 开发促进侧枝生长的血管生成疗法。这个 这些实验的动物模型包括放置一个紫红色的 猪冠状动脉左回旋支封堵器制作 逐渐的冠状动脉闭塞。将决定是否管理 生长因子(碱性成纤维细胞生长因子和血管内皮生长因子)联合肝素增强侧支循环 发展。第二个目标是确定分子机制。 它们在冠状动脉病变期间对心脏的血管生成起作用 动脉闭塞，从而阐明了潜在的刺激方法 血管生长。首席调查员的初步证据 提示血管内皮生长因子参与了侧支循环的合成。校长 调查员将通过尝试建立一个 血管内皮生长因子的表达与血液的因果关系 心脏中的血管合成。将在这两个方面进行研究 动物模型和培养的心肌细胞。体内研究将 包括使用流动探头，这将允许监测程度 冠状动脉闭塞的分子、生理和形态 事件可以相互关联。这些研究将涉及测量 微球流动，血管内皮生长因子和其他生长因子的测定 通过原位和溶液杂交，形态计量学分析， 和免疫组织化学。体外研究将涉及暴露于 细胞对低氧条件的反应，并检测血管内皮生长因子的分泌和 血管生成特性。最后，研究了基因启动子序列。 反应将通过使用启动子/报告嵌合体在两者中进行检查 培养的细胞和完整的心脏。

DESCRIPTION: Survival of the ischemic heart is dependent on the growth of the collateral circulation. However, collateral development is frequently not sufficient to fully meet the blood supply needs of the compromised myocardium. One of the goals of this research team is to develop angiogenic therapies which promote collateral growth. The animal model for these experiments consists of placing an amaroid occluder on the left circumflex coronary artery of pigs to produce gradual coronary occlusion. It will be determined if administration of growth factors (bFGF and VEGF) combined with heparin enhances collateral development. A second goal is to identify the molecular mechanisms which are responsible for angiogenesis in the heart during coronary artery occlusion and thus elucidated potential approaches for stimulating blood vessel growth. The principal investigator's preliminary evidence suggests that VEGF is involved in collateral synthesis. The principal investigator will extend this observation by attempting to establish a cause and effect relationship between expression of VEGF and blood vessel synthesis in the heart. Studies will be performed in both this animal model and in cultured cardiomyocytes. The in vivo studies will involve a use of a flow probe which will permit monitoring the degree of coronary occlusion so that molecular, physiologic, and morphologic events can be correlated. These studies will involve measurements of flow with microspheres, measurement of VEGF and other growth factor expression by in-situ and solution hybridization, morphometric analysis, and immunohistochemistry. The in vitro studies will involve exposure of cells to hypoxic conditions and examining VEGF secretion and angiogenic properties. Lastly, promoter sequences involved in the response will be examined by use of promoter/reporter chimeras in both cultured cells and in intact hearts.