MECHANISM OF COCAINE INDUCED ATHEROGENESIS

可卡因诱发动脉粥样硬化的机制

• 批准号: 3424258
• 负责人: Renu Virmani
• 金额: $ 5.62万
• 依托单位: AMERICAN REGISTRY OF PATHOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-12-13 至 1993-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3424258
• 关键词: B lymphocyte; T lymphocyte; aorta; atherosclerosis; atherosclerotic plaque; cocaine; coronary artery; cytokine; cytotoxic T lymphocyte; disease /disorder proneness /risk; helper T lymphocyte; histopathology; human tissue; image processing; immunocytochemistry; macrophage; mast cell; muscle cells; natural killer cells; postmortem; smooth muscle; tissue /cell preparation

Illicit use of cocaine has reached epidemic proportions in most major cities in the USA and at least 4 to 5 million Americans use it regularly. Cocaine has been clinically described to cause myocardial ischemia and infarction, coronary thrombosis and sudden cardiac death. We have observed in a preliminary study on "Pathobiologic determinants of atherosclerosis in youth" that the thoracic and abdominal aorta from young cocaine associated death victims (19 patients) had increased sudanophilia in the absence of well known risk factors compared to non-cocaine associated trauma related deaths (17 pts). Also, in another study, severe coronary atherosclerosis (>75% cross-sectional area luminal narrowing) occurred in 5 of 6 patients who died with cocaine associated thrombosis (mean age 29 + 6 years). The atherosclerotic plaques were rich in macrophages and smooth muscle cells. Acute and chronic inflammatory cells (T and B cells) were seen within intima, media, and adventitia suggestive of an immunologically mediated injury. Therefore, we propose to expand these observations to determine the role of cocaine in atherogenesis. In the aortas and coronary arteries of young (15-44 years) cocaine and noncocaine-associated death victims we will: 1. determine the role of cocaine and other drugs of abuse in the initiation and progression of atherosclerosis and their relationship to the usual risk factors. 2. determine the presence and extent of macrophages; B and T lymphocytes; mast cells and smooth muscle cells utilizing immunohistochemical techniques and computerized image processing and their relationship to cocaine and other risk factors. 3. subtype T cells into CD4 (inducer) and CD8 (cytotoxic), and natural killer lymphocytes, and determine if these may be present in different proportions in cocaine and noncocaine users. 4. determine the presence and role of cytokines (interleukin-1, tumor necrosis factor and interferon gamma) in atherosclerosis and if these are present in increased amounts in cocaine users. These studies will help us confirm our preliminary observations of accelerated atherogenesis in cocaine user, establish the relationship to other risk factors of atherogenesis, and clarify a mechanism of initiation and progression of atherosclerosis.

可卡因的非法使用在大多数主要的 美国的城市和至少4至500万美国人定期使用它。 可卡因在临床上被描述为引起心肌缺血和 梗塞，冠状动脉血栓形成和心脏猝死。 我们已经观察到 在一项关于动脉粥样硬化病原体决定因素的初步研究中 青年”是来自年轻可卡因的胸腔和腹主动脉 死亡受害者（19例患者）在没有 与非可卡因相关的创伤相比，众所周知的危险因素 死亡（17分）。 另外，在另一项研究中，严重的冠状动脉粥样硬化 （> 75％的横截面区域腔窄）发生在6例患者中的5例中 死于可卡因相关的血栓形成（平均年龄在29岁 + 6岁）中。 这 动脉粥样硬化斑块富含巨噬细胞和平滑肌细胞。 在内部看到急性和慢性炎性细胞（T和B细胞） Intima，Media和Addeditia暗示了免疫学介导的 受伤。 因此，我们建议扩大这些观察结果以确定 可卡因在动脉粥样硬化中的作用。 在主动脉和冠状动脉中 年轻（15-44岁）可卡因和与非卡因相关的死亡受害者我们 意志：1。确定可卡因和其他滥用药物在 动脉粥样硬化的启动和进展及其与 通常的风险因素。 2。确定巨噬细胞的存在和程度； B和T淋巴细胞；肥大细胞和平滑肌细胞利用 免疫组织化学技术和计算机图像处理及其 与可卡因和其他风险因素的关系。 3。亚型T细胞进入 CD4（诱导剂）和CD8（细胞毒性）以及天然杀手型淋巴细胞，以及 确定这些在可卡因中是否存在不同比例的存在，并且 非卡因用户。 4。确定细胞因子的存在和作用 （白介素-1，肿瘤坏死因子和干扰素γ） 动脉粥样硬化，如果可卡因的量增加 用户。 这些研究将帮助我们确认我们对 加速可卡因用户的动脉粥样硬化，建立与 动脉粥样硬化的其他危险因素，并阐明一种启动机制 和动脉粥样硬化的进展。