Pulmonary arterial hypertension: a disease of tethers, SNAREs and SNAPs?
Pulmonary arterial hypertension: a disease of tethers, SNAREs and SNAPs?
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DOI：
10.1152/ajpheart.01386.2006
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发表时间：
2007-07
期刊：
影响因子：
--
通讯作者：
P. Sehgal;Somshuvra Mukhopadhyay
中科院分区：
文献类型：
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作者：
P. Sehgal;Somshuvra Mukhopadhyay
在过去的四十年中，组织学和电镜研究强调了人类和实验性肺动脉高压（缺氧和单碱）肺动脉病变中“丰满”、“增大”的内皮、平滑肌和成纤维细胞成分，内质网、高尔基堆积和空泡化增加。然而，细胞膜内运输中断在本病病理生物学中的作用尚未得到足够的重视。最近的研究表明，在这种疾病的发展中，血管相关蛋白和细胞表面受体的细胞内运输中断的发病作用。本文的目的是强调膜系索、SNAREs和SNAPs对水疱运输的分子调控，并提出它们的功能障碍如何直接和/或间接地促进实验模型和人类肺动脉高压的发展，包括骨形态发生受体2型突变。
Histological and electron microscopic studies over the past four decades have highlighted "plump," "enlarged" endothelial, smooth muscle, and fibroblastic cellular elements with increased endoplasmic reticulum, Golgi stacks, and vacuolation in pulmonary arterial lesions in human and in experimental (hypoxia and monocrotaline) pulmonary arterial hypertension. However, the contribution of disrupted intracellular membrane trafficking in the pathobiology of this disease has received insufficient attention. Recent studies suggest a pathogenetic role of the disruption of intracellular trafficking of vasorelevant proteins and cell-surface receptors in the development of this disease. The purpose of this essay is to highlight the molecular regulation of vesicular trafficking by membrane tethers, SNAREs and SNAPs, and to suggest how their dysfunction, directly and/or indirectly, might contribute to development of pulmonary arterial hypertension in experimental models and in humans, including that due to mutations in bone morphogenetic receptor type 2.