PATHOGENESIS OF PULMONARY ARTERIOPATHY IN SIMIAN AIDS

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 我们在感染SIV或SIV的猕猴中观察到一种综合征，包括肺动脉病变、血小板减少症和右心室或肺动脉中潜在的致命血栓。 类似的问题也可能发生在HIV感染者身上，尽管这些问题之间没有明确的关系。 根据现有资料，尚不能确定该综合征的机制和发病机制。 该试点项目的目标是评估生物标志物和技术，这些生物标志物和技术可以在未来用于研究猕猴这种综合征的发病机制，并确定该模型在人类HIV相关并发症研究中的实用性。 一项涉及SHIV感染动物的实验已经完成，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志物评估剩余的23只动物。 技术标准化，并确定正常范围。 从两只发生肺动脉病的动物中采集有限的样本集，并在标准化评估前实施安乐死。 这些动物均显示心脏和凝血参数异常，表明这些参数将在未来的研究中有用。 组织学正在进行中，以确定这些参数与动脉病发展不同阶段的关系。

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.