DETERMINANTS OF CORONARY COLLATERAL DEVELOPMENT

描述：缺血性心脏的存活取决于心肌细胞的生长。 侧支循环 然而，抵押品开发是 通常不足以完全满足患者的血液供应需求。 心肌受损 这个研究小组的目标之一是 开发促进侧枝生长的血管生成疗法。 的 用于这些实验的动物模型包括将amaroid 在猪的左回旋支冠状动脉上的封堵器， 冠状动脉逐渐闭塞 将决定是否给予 生长因子（bFGF和VEGF）联合肝素可增强侧支循环 发展 第二个目标是确定 在冠状动脉粥样硬化的过程中， 动脉闭塞，从而阐明了刺激的潜在方法 血管生长 首席调查员的初步证据 提示VEGF参与侧枝合成。 校长 研究人员将通过尝试建立一个 血管内皮生长因子表达与血液流变学的因果关系 心脏血管合成 研究将在这两个方面进行。 动物模型和培养的心肌细胞中。 体内研究将 涉及使用流量探针，其将允许监测 冠状动脉闭塞的分子，生理和形态学 事件可以相互关联。 这些研究将涉及测量 微球流动，VEGF和其他生长因子的测量 通过原位和溶液杂交，形态测定分析， 和免疫组织 体外研究将涉及暴露 的细胞缺氧条件下，并检查VEGF分泌， 血管生成特性。 最后，参与转录的启动子序列， 将通过使用启动子/报告基因嵌合体在两种细胞中检测应答。 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.