Immune dysfunction and pulmonary hypertension in primate model of HIV infection

HIV感染灵长类动物模型中的免疫功能障碍和肺动脉高压

• 批准号: 9404231
• 负责人: Karen A Norris
• 金额: $ 23.85万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-03 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9404231
• 关键词: Immune; dysfunction; pulmonary; hypertension; primate

 DESCRIPTION (provided by applicant): Within the context of chronic HIV infection, pulmonary arterial hypertension (PAH) is a life-threatening complication characterized by pulmonary vascular remodeling, elevated pulmonary arterial pressure and right heart failure. Lack of understanding of the pathogenesis of HIV-PAH, along with deficiencies of available animal models, greatly impede identification and testing of new therapies. In this proposal, the overall objectives will focus on 1) determination of the role of chronic immune activation and inflammation on the development of PAH in a non-human primate model of HIV-PAH and 2) the evaluation of the effectiveness of anti-retroviral therapy, conventional PAH therapy and anti-inflammatory therapy in the primate model. These studies will not only address the mechanisms associated with the development of HIV-PAH, but they will provide critical information regarding the timing and targets that may be amenable to therapies aimed at both prevention and resolution of vascular damage, hemodynamic alterations and right heart dysfunction.

 描述（由申请方提供）：在慢性HIV感染的背景下，肺动脉高压（PAH）是一种危及生命的并发症，其特征为肺血管重塑、肺动脉压升高和右心衰竭。对HIV-PAH的发病机制缺乏了解，沿着可用动物模型的缺陷，极大地阻碍了新疗法的鉴定和测试。在本提案中，总体目标将集中于1）确定慢性免疫激活和炎症在非人灵长类HIV-PAH模型中PAH发展中的作用，以及2）评价灵长类模型中抗逆转录病毒治疗、常规PAH治疗和抗炎治疗的有效性。这些研究将不仅解决与HIV-PAH的发展相关的机制，但他们将提供关键信息的时间和目标，可能适合治疗，旨在预防和解决血管损伤，血流动力学改变和右心功能障碍。