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.

这个子项目是利用这些资源的众多研究子项目之一