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首页> 外文期刊>Pulmonary Circulation >Versican Accumulates in Vascular Lesions in Pulmonary Arterial Hypertension:
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Versican Accumulates in Vascular Lesions in Pulmonary Arterial Hypertension:

机译：Versican积累在肺动脉高压的血管病变中：

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Pulmonary arterial hypertension (PAH) is a lethal condition for which there is no effective curative pharmacotherapy. PAH is characterized by vasoconstriction, wall thickening of pulmonary arteries, and increased vascular resistance. Versican is a chondroitin sulfate proteoglycan in the vascular extracellular matrix that accumulates following vascular injury and promotes smooth-muscle cell proliferation in systemic arteries. Here, we investigated whether versican may play a similar role in PAH. Paraffin-embedded lung sections from patients who underwent lung transplantation to treat PAH were used for immunohistochemistry. The etiologies of PAH in the subjects involved in this study were idiopathic PAH, scleroderma, and congenital heart disease (atrial septal defect) with left-to-right shunt. Independent of the underlying etiology, increased versican immunostaining was observed in areas of medial thickening, in neointima, and in plexiform lesions. Western blot of lung tissue lysates confirmed accumulation of versican in patients with PAH. Double staining for versican and CD45 showed only occasional colocalization in neointima of high-grade lesions and plexiform lesions. In vitro, metabolic labeling with [35S]sulfate showed that human pulmonary artery smooth-muscle cells (hPASMCs) produce mainly chondroitin sulfate glycosaminoglycans. In addition, hypoxia, but not cyclic stretch, was demonstrated to increase both versican messenger RNA expression and protein synthesis by hPASMCs. Versican accumulates in vascular lesions of PAH, and the amount of versican correlates more with lesion severity than with underlying etiology or inflammation. Hypoxia is a possible regulator of versican accumulation, which may promote proliferation of pulmonary smooth-muscle cells and vascular remodeling in PAH.
机译：肺动脉高压（PAH）是一种致命疾病，目前尚无有效的药物治疗方法。 PAH的特征是血管收缩，肺动脉壁增厚和血管阻力增加。 Versican是血管外细胞基质中的硫酸软骨素蛋白聚糖，在血管损伤后会积聚并促进全身动脉中平滑肌细胞的增殖。在这里，我们调查了versican是否可能在PAH中起类似的作用。进行了肺移植治疗PAH的患者的石蜡包埋的肺切片用于免疫组化。参与这项研究的受试者的PAH病因是特发性PAH，硬皮病和先天性心脏病（房间隔缺损），并从左向右分流。与潜在病因无关，在内侧增厚区域，新内膜和丛状病变中观察到Verscan免疫染色增加。肺组织裂解物的蛋白质印迹证实了PAH患者中versican的积累。 versican和CD45的双重染色仅在高级别病变和丛状病变的新内膜中偶尔出现局部定位。在体外，用[35S]硫酸盐进行的代谢标记表明，人肺动脉平滑肌细胞（hPASMC）主要产生硫酸软骨素糖胺聚糖。此外，低氧，但不是周期性的拉伸，被证明可以通过hPASMCs增加versican Messenger的RNA表达和蛋白质合成。 Versican会在PAH的血管病变中积聚，而Versican的含量与病变严重程度的关系要大于与潜在病因或炎症的关系。低氧可能是versican积累的调节剂，可能促进PAH中肺平滑肌细胞的增殖和血管重塑。

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