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: 8172903
• 负责人: Sonia Castro Flores
• 金额: $ 6.58万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172903
• 关键词: Arterial Disorder; Cardiac; Chronic; Complex; Computer Retrieval of Information on Scientific Projects Database; Development; Disease; Frequencies; Funding; Grant; HIV; HIV Infections; Highly Active Antiretroviral Therapy; Human; Illicit Drugs; Individual; Infection; Institution; Life; Lung; Macaca; Macaca mulatta; Measurement; Modeling; Morbidity - disease rate; Pathogenesis; Play; Prevention strategy; Pulmonary Hypertension; Pulmonary artery structure; Research; Research Personnel; Resources; Role; SIV; Source; Syndrome; Tissues; United States National Institutes of Health; Vascular Diseases; Vertebral column; Viral; World Health Organization; arterial lesion; human morbidity; mortality; nef Genes; pulmonary arterial hypertension; pulmonary function

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 根据世界卫生组织的数据，艾滋病毒是全球人类发病率和死亡率的头号原因。发达国家越来越多地使用高效抗逆转录病毒疗法，导致艾滋病毒感染者的发病率下降和存活率增加。存活率增加的一个后果是出现了艾滋病毒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，HIV肺动脉病的发病机制尚不清楚，限制了治疗和预防策略的发展。对HIV与人类肺动脉高压的发展之间的关系的理解有许多局限性。这些问题包括难以对自然感染过程中的心肺功能进行连续测量、使用非法药物或可能对心脏有害的药物。 先前的研究表明，感染了SHIV-nef的恒河猴出现了复杂的丛状肺动脉病变，类似于HIV相关性肺动脉高压。SHIV-nef是在猿猴免疫缺陷病毒骨架中含有HIV nef基因的嵌合病毒结构。相比之下，感染了非嵌合猿猴免疫缺陷病毒(SIV)的恒河猴没有出现与HIV感染者相似的肺动脉病变。这些发现表明，nef基因在这种威胁生命的疾病的发展中起着关键作用。本研究的目的是试图揭示HIV nef基因导致复杂的肺动脉疾病的细胞机制。我们希望通过了解感染新城疫病毒的猕猴发生肺血管疾病的机制，能够开发出针对这种综合征的治疗和预防策略。