SCOR - ISCHEMIC HEART DISEASE IN BLACKS

威斯康星医学院黑人缺血性心脏病的SCOR代表了一项多学科的建议，专注于解决这种病理基础(生理、分子和遗传)和临床(生理和遗传)问题。我们将我们的努力集中在糖尿病心脏病上，因为这种疾病在黑人人群中几乎是流行病，特别是那些被证实患有冠状动脉疾病的人，但它们也可能阻止患者的侧枝生长，并加剧心肌缺血的有害后果。我们的项目由4个项目和2个核心设施组成。我们的策略是使用与传统方法不同的实验方法来研究问题，并利用确凿的实验工具在一个水平上检验假说(记录生理或病理生理反应)，然后在细胞、离子挑战分子和/或遗传水平上阐明基本机制。项目1和2研究冠状动脉侧支循环的机制。项目1“冠脉对缺血适应的综合分析”将描绘生长因子及其各自的受体从侧支形成的起始阶段到最后阶段的表达的时间序列。该项目还阐明了糖尿病影响冠状动脉侧枝生长的机制。项目2(冠状动脉疾病和冠脉侧支的遗传基础)将定义黑人和白人患者冠状动脉疾病和冠脉侧支的遗传基础。该项目还将研究与冠状动脉疾病有关的等位基因的家族性传播。在项目3“氧化应激与人类冠脉微血管功能”中，糖尿病对血管功能的影响，血管上皮细胞取自黑白患者的心脏。我们还将利用大鼠的分子品系：耐缺血的Brown挪威和对缺血敏感的Dah，以及对缺血敏感的Dahl(项目4：心脏保护的分子遗传学)。Dahl株也是胰岛素抵抗的，并表现出盐敏感型高血压。这两个核心将作为数据和管理以及数据分析的储存库。行政管理核心将包含一个集中存储所有结果的文件服务器，所有调查员都可以进入。生物统计核心将分析所有的实验结果，并执行表型与基因的关联分析。我们相信，该计划产生的科学成果将为治疗缺血性心脏病的合理药物疗法提供模板，并将阐明导致黑人缺血性心脏病的机制。

The SCOR in Ischemic Heart Disease in Blacks at the Medical College of Wisconsin represents a multi-disciplinary proposal that focuses on solving basic (physiological, molecular, and genetic) and clinical (physiological and genetic) problems underlying this pathology. We have focused our efforts on diabetic heart disease, because this disease is of near epidemic proportions in the Black population, especially those with proven coronary artery disease, but they may also abrogate collateral growth in patients and augment the deleterious consequences of myocardial ischemia. Our program is composed of 4 Projects and 2 Core Facilities. Our strategy is to use experimental approaches that deviate from traditional methods to investigate the problems and to utilize corroborative experimental tools to test hypotheses at one level (documentation of physiological or pathophysiological responses) and then elucidate fundamental mechanisms at cellular, ion challenge molecular, and/or genetic levels. Projects 1 and 2 study mechanisms of coronary collateralization. Project 1, "Integrative Analysis of Coronary Adaptations to Ischemia" will delineate the temporal sequence of expression of growth factors, and their respective receptors from the initiation to the final stages of collateralization in dogs. This project also elucidate the mechanisms by which diabetes compromises coronary collateral growth. Project 2 (Genetic Basis of Coronary Artery Disease and Coronary Collateralization) will define the genetic basis of coronary artery disease and coronary collateralization in Black and White patients. This project will also examine the familial transmission of alleles involved in coronary artery disease. In Project 3, "Oxidant Stress and Human Coronary Microvascular Function," the effects of diabetes on vascular function, vessels on vascular cells obtained from human hearts of Black and White patients. We will also utilize molecular strains of rats: Brown Norway, which are resistant to ischemia and Dah, which are sensitive to ischemia and Dahl, which are sensitive to ischemia (Project 4: "Molecular Genetics of Cardioprotection"). The Dahl strain is also insulin resistant and demonstrates salt sensitive hypertension. The two cores will be involved as repositories for data and administration, and data analysis. The Administration Core will contain a centralized file server for all results and will be accessible to all investigators. The Biostatistics Core will analyze all experimental results, and perform the association analyses of phenotype with genotype. We believe the science generated by this program will provide the template for rational pharmacological therapies to treat ischemic heart disease and will elucidate mechanisms contributing to ischemic heart disease in Blacks.