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首页> 外文期刊>American Journal of Physiology >Golgi dysfunction is a common feature in idiopathic human pulmonary hypertension and vascular lesions in SHIV-nef-infected macaques.
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Golgi dysfunction is a common feature in idiopathic human pulmonary hypertension and vascular lesions in SHIV-nef-infected macaques.

机译：高尔基功能障碍是特发性人类肺动脉高压和SHIV感染的猕猴的血管病变的常见特征。

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Golgi dysfunction has been previously investigated as a mechanism involved in monocrotaline-induced pulmonary hypertension (PAH). In the present study, we addressed whether Golgi dysfunction might occur in pulmonary vascular cells in idiopathic PAH (IPAH) and whether there might be a causal relationship between trafficking dysfunction and vasculopathies of PAH. Quantitative immunostaining for the Golgi tethers giantin and p115 on human lung tissue from patients with IPAH (n = 6) compared with controls demonstrated a marked cytoplasmic dispersal of giantin- and p115-bearing vesicular elements in vascular cells in the proliferative, obliterative, and plexiform lesions in IPAH and an increase in the amounts of these Golgi tethers/matrix proteins per cell. The causality question was approached by genetic means using human immunodeficiency virus (HIV)-Nef, a protein that disrupts endocytic and trans-Golgi trafficking. Macaques infected with a chimeric simian immunodeficiency virus (SIV) containing the HIV-nef gene (SHIV-nef), but not the nonchimeric SIV virus containing the endogenous SIV-nef gene, displayed pulmonary arterial vasculopathies similar to those in human IPAH. Giantin and p115 levels and their subcellular distribution in pulmonary vascular cells in lungs of SHIV-nef infected macaques (n = 4) were compared with SIV-infected (n = 3) and an uninfected macaque control. Only macaques infected with chimeric SHIV-nef showed pulmonary vascular lesions containing cells with dramatic cytoplasmic dispersal and an increase in giantin and p115. Specifically, the HIV-Nef-positive cells showed increased giantin, p115, and the activated transcription factor PY-STAT3. These data represent the first test of the Golgi dysfunction hypothesis in IPAH and place trafficking and Golgi disruption in the chain of causality of pulmonary vasculopathies in the macaque model.
机译：高尔基功能障碍先前已被研究为一药作用，其可能与一丁烯茶碱诱发的肺动脉高压（PAH）有关。在本研究中，我们探讨了特发性PAH（IPAH）的肺血管细胞中是否可能发生高尔基功能障碍，以及运输功能障碍与PAH的血管病变之间是否存在因果关系。 IPAH（n = 6）患者与人对照在人肺组织上高尔基系链巨蛋白和p115的定量免疫染色与对照组相比，在增殖，闭塞和丛状的血管细胞中，含巨蛋白和p115的囊泡成分明显分布在细胞质中IPAH损伤和每个细胞中这些高尔基系链/基质蛋白的数量增加。使用人类免疫缺陷病毒（HIV）-Nef通过遗传手段解决了因果关系问题，Nef是一种破坏内吞和反高尔基贩运的蛋白质。猕猴感染了含有HIV-nef基因（SHIV-nef）的嵌合猿猴免疫缺陷病毒（SIV），但未感染含有内源性SIV-nef基因的非嵌合SIV病毒，显示出与人IPAH相似的肺动脉血管病变。比较了感染SHIV的猕猴（n = 4）与未感染SIV的猕猴（n = 3）中肺巨蛋白和p115水平及其在肺血管细胞中的亚细胞分布。只有感染了嵌合SHIV-nef的猕猴才显示出肺血管病变，其中含有具有明显胞质分散性的细胞，并且巨蛋白和p115含量增加。具体地说，HIV-Nef阳性细胞显示巨蛋白，p115和活化的转录因子PY-STAT3增加。这些数据代表了对IPAH中高尔基功能障碍假说的首次检验，并且在猕猴模型中将运输和高尔基体破坏置于肺血管病变的因果关系链中。

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