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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 根据世界卫生组织的说法，艾滋病毒是全球人类发病率和死亡率的第一名。发达国家中高度活跃的抗逆转录病毒疗法的使用增加导致发病率降低和HIV感染个体的存活率增加。这种增加的结果之一是新组织特异性表现的出现，包括肺动脉高压。慢性艾滋病毒感染的肺并发症现在以增加的频率认识到。目前，艾滋病毒肺动脉疾病的发病机理尚不清楚，限制了治疗和预防策略的发展。了解艾滋病毒与人类肺动脉高压的发展之间存在许多局限性。这些很难在自然感染过程中对心脏和肺功能进行连续测量，使用可能具有心脏毒性的非法药物或药物。 先前的研究表明，感染SHIV-NEF的恒河猕猴是一种嵌合病毒构建体，该病毒构建体，该病毒构建体中含有HIV Nef基因的猿猴免疫缺陷病毒骨架骨架形成了复杂的丛膜，如肺动脉病变，类似于与HIV相关肺相关的肺高血压相似的肺动脉动脉病变。相比之下，感染了非肾小球免疫缺陷病毒（SIV）的恒河猕猴没有发展与HIV感染个体中发生的肺动脉病变相似。这些发现表明，NEF基因在这种威胁生命状况的发展中起着关键作用。这项研究的目的是试图引起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感染猕猴中肺血管疾病发展的机制，可以开发该综合征的治疗和预防策略。