Objective

Reportedly, nestin was re-expressed in proliferative synthetic-type pulmonary artery smooth muscle cells (PASMCs) and obligatory for PASMC proliferation in pulmonary arterial hypertension (PAH). Accordingly, nestin is increased in pulmonary vascular lesions of congenital heart disease (CHD)-associated PAH patients. We tested the hypothesis whether nestin was re-expressed in proliferative synthetic-type PASMCs and associated with pulmonary vascular remodeling in CHD-PAH.

Materials and methods

Nestin expression was tested using lung tissues from CHD-PAH patients and monocrotaline (MCT) plus aortocaval (AV) shunt-induced PAH rats, human PASMCs (HPASMCs), and pulmonary artery endothelial cells (PAECs) and PASMCs from MCT-AV-induced PAH rats. The role and possible mechanism of nestin on HPASMC proliferation, apoptosis, cell cycle and migration were investigated by assays of CCK-8, EdU, TUNEL, flow cytometry, transwell chamber and immunoblotting assays.

Results

Nestin was solely expressed in proliferative synthetic-type PASMCs, but rarely detected in PAECs. Nestin was barely detected in normal pulmonary arterioles and occlusive pulmonary vascular lesions. Its expression was robustly increased in developing pulmonary vasculature, but returned to normal levels at the late stage of pulmonary vascular remodeling in lung tissues from CHD-PAH patients and MCT-AV-induced PAH rats. Besides, nestin peaks were consistent with the histological features in lung tissues of MCT-AV-induced PAH rats. Moreover, nestin overexpression effectively promoted HPASMC phenotypic transformation, proliferation, apoptosis resistance and migration via enhancing Wnt/β-catenin activation.

Conclusions

These data indicated that nestin was re-expressed in proliferative synthetic-type PASMCs and might represent a potential marker of pulmonary vascular remodeling in CHD-PAH.

中文翻译：

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巢蛋白是先天性心脏病相关肺动脉高压肺血管重塑的潜在标志物。

客观的

据报道，巢蛋白在增殖性合成型肺动脉平滑肌细胞 (PASMC) 中重新表达，并且是肺动脉高压 (PAH) 中 PASMC 增殖所必需的。因此，先天性心脏病 (CHD) 相关 PAH 患者的肺血管病变中巢蛋白增加。我们测试了巢蛋白是否在增殖性合成型 PASMC 中重新表达并与 CHD-PAH 中的肺血管重塑相关的假设。

材料和方法

使用来自 CHD-PAH 患者的肺组织和野百合碱 (MCT) 加主动脉 (AV) 分流诱导的 PAH 大鼠、人 PASMC (HPASMC) 和来自 MCT-AV 诱导的肺动脉内皮细胞 (PAEC) 和 PASMC 测试巢蛋白表达PAH 大鼠。通过CCK-8、EdU、TUNEL、流式细胞术、transwell小室和免疫印迹试验研究巢蛋白对HPASMC增殖、凋亡、细胞周期和迁移的作用和可能机制。

结果

巢蛋白仅在增殖合成型 PASMC 中表达，但在 PAEC 中很少检测到。在正常肺小动脉和闭塞性肺血管病变中几乎检测不到巢蛋白。它的表达在发育中的肺血管系统中显着增加，但在来自 CHD-PAH 患者和 MCT-AV 诱导的 PAH 大鼠的肺组织中肺血管重塑后期恢复到正常水平。此外，巢蛋白峰与 MCT-AV 诱导的 PAH 大鼠肺组织的组织学特征一致。此外，巢蛋白过表达通过增强 Wnt/β-catenin 活化有效促进 HPASMC 表型转化、增殖、抗凋亡和迁移。

结论

这些数据表明，巢蛋白在增殖性合成型 PASMC 中重新表达，可能代表 CHD-PAH 中肺血管重塑的潜在标志物。