PATHOGENESIS OF PULMONARY ARTERIOPATHY IN SIMIAN AIDS

猿猴艾滋病肺动脉病的发病机制

• 批准号: 8357629
• 负责人: CHARLOTTE HOTCHKISS
• 金额: $ 37.79万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357629
• 关键词: Animals; Arterial Disorder; Biological Markers; Coagulation Process; Congenital Heart Defects; Data; Development; Echocardiography; Funding; Future; Goals; Grant; HIV; Histopathology; Human; Investigation; Lung; Macaca; Macaca nemestrina; Modeling; National Center for Research Resources; Normal Range; Pathogenesis; Pilot Projects; Primates; Principal Investigator; Pulmonary artery structure; Research; Research Infrastructure; Resources; Right ventricular structure; SIV; Sampling; Simian Acquired Immunodeficiency Syndrome; Source; Staging; Syndrome; Techniques; Thrombocytopenia; Thrombus; United States National Institutes of Health; cost; research study; simian human immunodeficiency virus

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We have observed a syndrome in Macaca nemestrina infected with SIV or SHIV, consisting of pulmonary arteriopathy, thrombocytopenia, and potentially fatal thrombi in the right ventricle or pulmonary artery. Similar problems can occur in HIV-infected humans, although no clear relationship among the problems has been demonstrated. The mechanism and pathogenesis of this syndrome cannot be determined from the data currently available. The goal of this pilot project is to assess biomarkers and techniques which can be used in the future to investigate the pathogenesis of this syndrome in macaques, and determine the utility of this model in the investigation of HIV-related complications in humans. An experiment involving SHIV-infected animals reached completion, and we were able to assess the 23 remaining animals using echocardiography and a panel of coagulation biomarkers at three monthly timepoints. Techniques were standardized and normal ranges determined. Limited sample sets were collected from two animals that developed pulmonary arteriopathy and were euthanized prior to standardized assessment. These animals both displayed abnormalities of the heart and of coagulation parameters, suggesting that these parameters will be useful in future studies. Histopathology is underway to determine the relationship of these parameters to different stages in the development of arteriopathy.

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 我们已经观察到感染SIV或SIV的猕猴的一种综合征，包括肺动脉病变、血小板减少，以及潜在的致命性右室或肺动脉血栓。类似的问题也可能发生在感染艾滋病毒的人身上，尽管这些问题之间还没有明确的关系被证明。从目前可用的数据无法确定这种综合征的机制和发病机制。这一试点项目的目标是评估未来可用于研究猕猴这种综合征的发病机制的生物标志物和技术，并确定该模型在人类艾滋病毒相关并发症调查中的应用。 一项涉及SHIV感染动物的实验接近完成，我们能够在三个月的时间点使用超声心动图和一组凝血生物标记物评估其余23只动物。技术被标准化，正常范围被确定。有限的样本集从两只发展为肺动脉病的动物身上收集，并在标准化评估之前被安乐死。这些动物都表现出心脏和凝血参数的异常，这表明这些参数将在未来的研究中有用。组织病理学正在进行中，以确定这些参数与动脉病变发展的不同阶段的关系。