Immune dysfunction and pulmonary hypertension in primate model of HIV infection

 描述(申请人提供)：在慢性HIV感染的背景下，肺动脉高压(PAH)是一种威胁生命的并发症，其特征是肺血管重构、肺动脉压升高和右心衰竭。缺乏对HIV-PAH发病机制的了解，以及现有动物模型的不足，极大地阻碍了新疗法的识别和测试。在这项提案中，总体目标将集中在1)在非人类灵长类动物模型中确定慢性免疫激活和炎症在PAH发生中的作用，以及2)在灵长类动物模型中评估抗逆转录病毒治疗、常规PAH治疗和抗炎治疗的有效性。这些研究不仅将解决与HIV-PAH发展相关的机制，而且将提供关于可能适合于预防和解决血管损伤、血流动力学改变和右心功能障碍的治疗的时机和目标的关键信息。

 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.