VIRAL-HOST INTERACTIONS IN SIV CARDIAC DYSFUNCTION

点击翻译按钮获取中文摘要

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. HIV-associated cardiomyopathy is a frequent and serious HIV complication, yet the underlying pathophysiology is poorly understood. The central hypothesis of this proposal is that functional cardiac impairment that develops in SIV-infected macaques results from both increased synthesis and activation of selective matrix metalloproteinases (MMPs) associated with macrophage activation driven by SIV infection in the heart. There are 3 specific aims: Aim One: To determine the evolution of cardiac dysfunction in SIV-infected macaques based on comprehensive serial echoDoppler and pressure-volume relation analysis and to define the relationship between cardiac dysfunction and inflammatory responses in the heart including myocardial macrophage activation. Aim Two: To determine whether replication of macrophage-tropic SIV strains in the heart is a prerequisite for the development of cardiac dysfunction. Aim Three: To determine whether activation of matrix metalloproteinases are stimulated by SIV-infection of macrophages in the heart and lead to cardiac dysfunction. These studies will set the stage for performing interventive studies in SIV-infected macaques using approaches to target specific MMPs to prevent cardiac dysfuncti