SCOR - ISCHEMIC HEART DISEASE IN BLACKS

威斯康星医学院黑人缺血性心脏病SCOR代表了一个多学科的建议，重点解决这种病理学背后的基础（生理、分子和遗传）和临床（生理和遗传）问题。我们的研究重点是糖尿病性心脏病，因为这种疾病在黑人人群中几乎是流行病，尤其是那些已证实患有冠状动脉疾病的人，但它们也可能消除患者的侧枝生长，并增加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。我们的策略是使用偏离传统方法的实验方法来研究问题，并利用确证实验工具在一个层面（生理或病理生理反应的记录）测试假设，然后阐明细胞，离子挑战分子和/或遗传水平的基本机制。项目1和项目2研究冠状动脉侧支的机制。项目1，“冠状动脉缺血适应性的综合分析”将描述犬从侧枝化开始到最后阶段生长因子及其受体表达的时间序列。该项目还阐明了糖尿病损害冠状动脉侧枝生长的机制。项目2（冠状动脉疾病和冠状动脉侧支的遗传基础）将定义黑人和白人患者冠状动脉疾病和冠状动脉侧支的遗传基础。该项目还将研究与冠状动脉疾病有关的等位基因的家族传播。在Project 3，“氧化应激与人类冠状动脉微血管功能”中，糖尿病对血管功能的影响，血管对从黑人和白人患者心脏获得的血管细胞的影响。我们还将利用大鼠分子品系：抗缺血的Brown Norway和对缺血敏感的Dah和对缺血敏感的Dahl （Project 4：“molecular Genetics of Cardioprotection”）。Dahl菌株也具有胰岛素抵抗和盐敏感性高血压。这两个核心将作为数据和管理以及数据分析的存储库。行政核心将包含一个集中的文件服务器，用于所有结果，所有调查人员都可以访问。生物统计核心将分析所有实验结果，并进行表型与基因型的关联分析。我们相信这个项目产生的科学将为合理的药物治疗缺血性心脏病提供模板，并将阐明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.