DEVELOPMENT OF A RHESUS MACAQUE MODEL OF HIV ASSOCIATED PULMONARY HYPERTENSION

HIV相关肺动脉高压的恒河猴模型的建立

• 批准号: 8357983
• 负责人: Sonia Castro Flores
• 金额: $ 6.84万
• 依托单位: HARVARD MEDICAL SCHOOL
• 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/8357983
• 关键词: Arterial Disorder; Cardiac; Chronic; Complex; Development; Disease; Frequencies; Funding; Grant; HIV; HIV Infections; Highly Active Antiretroviral Therapy; Human; Illicit Drugs; Individual; Infection; Life; Lung; Macaca; Macaca mulatta; Measurement; Modeling; Morbidity - disease rate; National Center for Research Resources; New England; Pathogenesis; Play; Prevention strategy; Primates; Principal Investigator; Pulmonary Hypertension; Pulmonary artery structure; Research; Research Infrastructure; Resources; SIV; Source; Syndrome; Tissues; United States National Institutes of Health; Vascular Diseases; Vertebral column; Viral; World Health Organization; arterial lesion; base; cost; human morbidity; human mortality; nef Genes; pulmonary arterial hypertension; pulmonary function; simian human immunodeficiency virus; treatment strategy

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. According to the world health organization HIV is the number one cause of human morbidity and mortality worldwide. The increased use of highly active antiretroviral therapy in the developed world has resulted in a decrease in morbidity and increase in survival of HIV infected individuals. One consequence of this increased survival is the emergence of new tissue specific manifestations of HIV infection, including pulmonary arterial hypertension. Pulmonary complications of chronic HIV infection are now being recognized with increasing frequency. Currently the pathogenesis of HIV pulmonary arteriopathy is poorly understood, limiting the development of both treatment and prevention strategies. There are numerous limitations in understanding of the relationship between HIV and the development of pulmonary hypertension in humans. These include difficulty in making serial measurements of cardiac and pulmonary function over the natural course of infection, the use of illicit drugs or agents that may be cardiotoxic. Prior studies have shown that rhesus macaques infected with SHIV-nef which is a chimeric viral construct containing the HIV nef gene in a Simian immunodeficiency virus backbone developed complex plexiform like pulmonary arterial lesions similar to those see in HIV associated pulmonary hypertension. In contrast, rhesus macaques infected with a non-chimeric Simian immunodeficiency virus (SIV) did not develop pulmonary arterial lesions similar to those occurring in HIV infected individuals. These findings suggest that the nef gene plays a key role in the development of this life threatening condition. The aim of this study is to try to elicit the cellular mechanisms by which the HIV nef gene induces complex pulmonary artery disease. We hope that by understanding the mechanisms involved in the development of pulmonary vascular disease in SHIV-nef infected macaques that both treatment and prevention strategies for this syndrome can be developed.

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。 根据世界卫生组织的数据，艾滋病毒是人类发病的头号原因， 全世界的死亡率。发达国家更多地使用高效抗逆转录病毒疗法，降低了艾滋病毒感染者的发病率，提高了其存活率。这种存活率增加的一个后果是出现了HIV感染的新的组织特异性表现，包括肺动脉高压。慢性艾滋病毒感染的肺部并发症现在越来越多地被认识到。目前对HIV肺动脉病的发病机制了解甚少，限制了治疗和预防策略的发展。在理解HIV与人类肺动脉高压发展之间的关系方面存在许多局限性。这些包括在感染的自然过程中难以连续测量心脏和肺功能，使用非法药物或可能对心脏有毒的药物。 先前的研究表明，感染了SHIV-nef的恒河猴（猴免疫缺陷病毒骨架中含有HIV nef基因的嵌合病毒构建体）会产生复杂的丛状结构 如肺动脉病变，类似于艾滋病相关的肺动脉高压。与此相反，感染了非嵌合的猿猴免疫缺陷病毒（SIV）的恒河猴并没有出现与HIV感染者相似的肺动脉病变。这些发现表明nef基因在这种危及生命的疾病的发展中起着关键作用。本研究的目的是试图引出HIV nef基因诱导复杂肺动脉疾病的细胞机制。我们希望通过了解SHIV-nef感染的猕猴肺血管疾病发展的机制，可以开发这种综合征的治疗和预防策略。