BIOLOGICAL MEDIATORS OF ATHEROGENESIS IN BLACK AMERICANS

冠心病（Coronary heart disease，CHD）是导致发病和死亡的主要原因 也是黑人死亡的主要原因 美国人 然而，越来越多的证据表明， 与白人相比，CHD患病率增加。 这个项目的总体目标是 应用程序的目的是确定机制的差异， 黑人与白人CHD的发生，以了解 CHD发病率的种族差异。 该项目将重点确定 参与动脉粥样硬化前早期的重要细胞和分子 可能介导局部炎症反应和肿瘤生长的病变 血管壁 更多的研究将侧重于正在进行的 通过对成熟动脉粥样硬化和动脉粥样硬化的分析， 血管壁对治疗性介入手术的反应， 血管成形术 这些项目将整合脂质代谢的研究 单核细胞/白细胞粘附和迁移到血管壁中 和动脉粥样硬化斑块的发展。 具体来说，我们将测试 以下假设：a）种族差异 餐后脂质代谢; B）改变餐后脂质 代谢对单核细胞/白细胞粘附有急性影响， 通过改变局部血管壁的作用， 趋化因子或粘附受体的表达; c）存在 黑人血管壁的细胞和/或分子差异 可以解释动脉粥样硬化形成的种族差异。 在 此外，这些研究将重新检查单克隆假说， 动脉粥样硬化斑块发展的细胞特征 葡萄糖-6-磷酸酶特异性亚型的分布 黑色素瘤早期脂肪条纹和成熟动脉粥样硬化中的脱氢酶 雌性使用同种型特异性探针进行原位杂交。 这 将使我们能够确定动脉粥样硬化斑块是否起源于单一的 或多个细胞事件，通过表征 早期脂肪条纹以及晚期动脉粥样硬化。

Coronary heart disease (CHD) is the major cause of morbidity and mortality in the United States and is also the leading cause of death among black Americans. However, there is increasing evidence that blacks show an increased prevalence of CHD compared to whites. The overall goal of this application is to identify differences in the mechanisms underlying the genesis of CHD in blacks versus whites in order to understand the basis for racial differences in rates of CHD. This project will focus on identifying the important cells and molecules involved in the early pre-atherosclerotic lesion that might mediate local inflammatory responses and growth of the vessel wall. Additional studies will focus on the ongoing process of intimal development through an analysis of mature atheromas and the response of the vessel wall to a therapeutic interventional procedure, angioplasty. These projects will integrate studies of lipid metabolism with monocyte/leukocyte adhesion and transmigration into the vessel wall and atherosclerotic plaque development. Specifically we will test the following hypotheses: a) that there are racial differences in the postprandial metabolism of lipids; b) that altered postprandial lipid metabolism has acute effects on monocyte/leukocyte adhesion and transmigration into the vessel wall through actions modifying the local expression of chemotactic factors or adhesion receptors; c) that there are cellular and/or molecular differences in the vessel wall in blacks compared to whites that might explain racial differences in atherogenesis. In addition these studies will re-examine the monoclonal hypothesis regarding atherosclerotic plaque development by characterizing the cellular distribution of specific isoforms of the glucose-6-phosphatase dehydrogenase enzyme in early fatty streaks and mature atheromas of black females using in situ hybridization with isoform specific probes. This will allow us to determine if atherosclerotic plaques originate from single or multiple cellular event(s) by characterizing zones of monoclonality in early fatty streaks as well as in late atheromas.