CARDIOVASCULAR DYSFUNCTION AND NO CONTROL IN MURINE AIDS

鼠类艾滋病的心血管功能障碍和无法控制

• 批准号: 2796819
• 负责人: John Anthony Bauer
• 金额: $ 14.6万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-30 至 2002-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2796819
• 关键词: AIDS; Retroviridae disease; antioxidants; cardiovascular function; disease /disorder model; echocardiography; heart metabolism; histopathology; immunopathology; laboratory mouse; myocardium disorder; nitric oxide; oxidative stress; tumor necrosis factor alpha

DESCRIPTION (Adapted from applicant's abstract) Several recent studies have shown that cardiovascular dysfunction may be an important complication of HIV infection, but the exact incidence of this problem, and the mechanism(s) by which it develops have not been defined. Evidence of increased reactive oxygen intermediates (R0I's) has been found in blood and tissues of HIV patients and animal models of retroviral infection; these conditions have been implicated in HIV viral activation, cytokine production, and immune system dysfunction. As a free radical and potent oxidant (particularly when combined with superoxide anion), NO has recently been implicated in AIDS-related neurotoxicity and dementia. It is therefore possible that important changes in NO production or destruction processes may play a role in retroviral immunopathogenesis, particularly in cardiovascular complications. The long term objectives are to determine the mechanism(s) of retrovirus related cardiovascular complications, define the role(s) of NO in these changes, and examine how can they be prevented or resolved. A relevant and well-documented mouse model of retroviral infection that has been shown to develop cardiac damage during infection will be studied. In vivo cardiac dysfunction will be related to cardiac oxidative damage during retroviral infection, and changes in balance between NO production and destruction pathways will be examined during immunopathogenesis and cardiac impairment. The investigators will also design and test rational strategies to intervene. In related investigations they will determine the relation of endogenous NO in expired air to cardiovascular and pulmonary complications in HIV infected patients. These studies will provide important new information regarding the mechanisms of cardiac dysfunction in retroviral infection, and provide important new insights and strategies for an emerging problem. (End of Abstract)

描述 （改编自申请人的摘要）最近的几项研究表明 心血管功能障碍可能是艾滋病毒的重要并发症 感染，但该问题的确切发生率以及机制 它开发的内容尚未定义。 反应性增加的证据 在 HIV 的血液和组织中发现了氧中间体（R0I's） 逆转录病毒感染的患者和动物模型；这些条件有 与 HIV 病毒激活、细胞因子产生和免疫有关 系统功能障碍。 作为自由基和强氧化剂（特别是当 与超氧阴离子结合），NO 最近被认为与 艾滋病相关的神经毒性和痴呆。 因此有可能 NO产生或破坏过程的重要变化可能发挥作用 逆转录病毒免疫发病机制，特别是心血管疾病 并发症。 长期目标是确定机制 逆转录病毒相关的心血管并发症，定义 NO 的作用 并研究如何预防或解决这些变化。 一个 相关且有据可查的逆转录病毒感染小鼠模型 已被证明在感染期间会造成心脏损伤的研究将被研究。 在 体内心脏功能障碍将与心脏氧化损伤有关 逆转录病毒感染，以及 NO 产生和平衡之间的变化 将在免疫发病机制和心脏疾病过程中检查破坏途径 损害。 研究人员还将设计和测试合理的策略 进行干预。 在相关调查中，他们将确定以下关系： 呼出气中的内源性 NO 与心血管和肺部并发症的关系 在艾滋病毒感染者中。 这些研究将提供重要的新 有关逆转录病毒引起的心脏功能障碍机制的信息 感染，并为新兴疾病提供重要的新见解和策略 问题。 （摘要完）