Department of Molecular and Comparative Pathobiology, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
AIDS. 2012 Apr 24;26(7):815-23. doi: 10.1097/QAD.0b013e3283518f01.
To establish the relationship between HIV-induced cardiac diastolic dysfunction, immune responses, and virus replication in the heart using the simian immunodeficiency virus (SIV)/macaque model.
Cardiac diastolic dysfunction is common in HIV-infected individuals including asymptomatic patients and those treated with combination antiretroviral therapy. SIV-infected macaques develop cardiac dysfunction, serving as a useful model to establish mechanisms underlying HIV-induced cardiac dysfunction. To understand the relationship between functional cardiac impairment, viral replication in the heart, and associated host inflammatory responses, cardiac function was evaluated in SIV-infected macaques and functional decline was correlated with features of the host immune response and the extent of viral replication in both the myocardium and plasma.
Cardiac function was evaluated longitudinally in 22 SIV-infected and eight uninfected macaques using mitral inflow and tissue Doppler echocardiography. Myocardial macrophage populations were evaluated by CD68 and CD163 immunostaining. SIV RNA levels in both myocardium and plasma were measured by qRT-PCR.
Echocardiographic abnormalities developed in SIV-infected macaques that closely resembled diastolic dysfunction reported in asymptomatic HIV-infected individuals. Although CD68 and CD163 were upregulated in the myocardium of SIV-infected animals, neither macrophage marker correlated with functional decline. SIV-induced diastolic dysfunction was strongly correlated with extent of SIV replication in the myocardium, implicating virus or viral proteins in the initiation and progression of cardiac dysfunction.
This study demonstrated a strong correlation between cardiac functional impairment and extent of SIV replication in the myocardium, suggesting that persistent viral replication in myocardial macrophages induces cardiomyocyte damage manifest as diastolic dysfunction.
利用猴免疫缺陷病毒（SIV）/猴模型，建立 HIV 引起的心脏舒张功能障碍、免疫反应与心脏病毒复制之间的关系。
心脏舒张功能障碍在 HIV 感染个体中很常见，包括无症状患者和接受联合抗逆转录病毒治疗的患者。感染 SIV 的猕猴会出现心脏功能障碍，因此是建立 HIV 引起的心脏功能障碍机制的有用模型。为了了解心脏功能损伤与心脏病毒复制以及相关宿主炎症反应之间的关系，我们对 SIV 感染的猕猴进行了心脏功能评估，并将功能下降与宿主免疫反应的特征以及心肌和血浆中的病毒复制程度相关联。
我们使用二尖瓣血流和组织多普勒超声心动图对 22 只 SIV 感染和 8 只未感染的猕猴进行了纵向心脏功能评估。通过 CD68 和 CD163 免疫染色评估心肌巨噬细胞群体。通过 qRT-PCR 测量心肌和血浆中的 SIV RNA 水平。
SIV 感染的猕猴出现了类似于无症状 HIV 感染个体报告的舒张功能障碍的超声心动图异常。尽管 SIV 感染动物的心肌中 CD68 和 CD163 上调，但这两种巨噬细胞标志物均与功能下降无关。SIV 引起的舒张功能障碍与心肌中的 SIV 复制程度密切相关，提示病毒或病毒蛋白在心脏功能障碍的起始和进展中起作用。
本研究表明，心脏功能损伤与心肌中 SIV 复制程度之间存在很强的相关性，提示心肌巨噬细胞中持续的病毒复制会导致心肌细胞损伤，表现为舒张功能障碍。
