INSULIN AND PATHOGENESIS OF ATHEROSCLEROSIS IN BLACKS

胰岛素与黑人动脉粥样硬化的发病机制

• 批准号: 2225831
• 负责人: Richard J Katz
• 金额: $ 31.84万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 1997-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2225831
• 关键词: African American; androgens; atherosclerosis; coronary disorder; disease /disorder proneness /risk; heart catheterization; heart circulation; hematology; human subject; hyperinsulinism; ultrasound blood flow measurement; vasomotion

Coronary artery disease (CAD) is the leading cause of morbidity and mortality among blacks. The purpose of this project is to investigate the potential central role of hyperinsulinemia in the pathogenesis of CAD in this ethnic group. Hyperinsulinemia has been associated with increased CAD risk and is commonly associated with glucose intolerance, hypertension, and obesity in blacks. High insulin or proinsulin may be atherogenic via several mechanisms including: 1) increased androgens in women, 2) coronary artery endothelial dysfunction, 3) vascular smooth muscle proliferation and 4) abnormalities of the coagulation and fibrinolytic system. We propose five overlapping studies to investigate multiple aspects of insulin action: 1) Using new assay techniques we will profile both insulin and proinsulin activity in blacks versus whites with catheterization documented premature CAD compared to normals. 2) Androgen status will be related to insulin/proinsulin profiles in black and white premenopausal women. 3) Endothelial-dependent vasoreactivity will be measured using new Doppler techniques in a subgroup of catheterized nonCAD blacks in relation to insulin/proinsulin profile. 4) using new immunochemistry techniques we will demonstrate any specific abnormalities of insulin binding and growth factors in atheroma and arterial segments of black and white CAD patients. 5) Using highly sensitive assays we will evaluate hematological effects associated with insulin abnormalities. This study will provide initial information that could shed light on specific mechanisms of CAD in blacks. Hopefully this data will help further development of new prevention and therapeutic trials.

冠状动脉疾病（CAD）是发病率和 黑人的死亡率。 该项目的目的是调查 高胰岛素血症在CAD发病机理中的潜在核心作用 在这个族裔中。 高胰岛素血症与CAD风险增加有关，IS 通常与葡萄糖不耐症，高血压和肥胖有关 在黑人中。 高胰岛素或促蛋白可能通过几种 包括：1）女性雄激素的机制，2）冠状动脉 内皮功能障碍，3）血管平滑肌增殖和4） 凝血和纤维蛋白水解系统的异常。 我们提出了五项重叠研究，以研究 胰岛素作用：1）使用新测定技术，我们将介绍两者 黑人与白人的胰岛素和促蛋白活性 导管插入与正常情况相比，记录了过早的CAD。 2）雄激素 状态将与黑白的胰岛素/促胰岛素概况有关 绝经前妇女。 3）内皮依赖性血管反应性将是 使用新的多普勒技术在导管插入的亚组中测量 与胰岛素/促硫素特征有关的非cad黑人。 4）使用新 免疫化学技术我们将证明任何特定异常 动脉瘤和动脉片段中胰岛素结合和生长因子的 黑白CAD患者。 5）使用高度敏感的测定法 评估与胰岛素异常相关的血液学作用。 这项研究将提供可能阐明的初始信息 黑色CAD的特定机制。 希望这些数据会有所帮助 进一步开发新的预防和治疗试验。