Background: Heritable pulmonary veno-occlusive disease (PVOD) is linked to mutations in the eukaryotic initiation factor 2 alpha kinase 4 (EIF2AK4) gene, leading to a loss of general control nonderepressible 2 (GCN2). The role of GCN2 expression in pulmonary vascular remodeling remains obscure.

GCN2 dysfunction led to an enhanced transcription of collagen I gene (col1a1 and col1a2) through decreasing ATF3-dependent p38 phosphorylation inhibition in PVOD, which promotes the collagen I synthesis in pulmonary arterial smooth muscle cells (PASMCs) and eventually leads to increased collagen deposition in pulmonary artery.

2024年10月5日 · EIF2AK4基因（编码GCN2）的隐性突变及其导致的GCN2蛋白表达减少与遗传性肺静脉阻塞病（PVOD）相关，这是一种罕见的严重肺动脉高压（PAH）亚型，特征为隔膜静脉和前隔膜小静脉的内膜增生和纤维化。 PVOD亚组的预后较经典PAH差，目前除了肺移植外没有有效治疗。 双等位基因EIF2AK4突变在25%的组织学确认的散发PVOD病例中发现。 虽然在特发性PAH（IPAH）患者中EIF2AK4突变较少见，但在一些遗传性PAH患者中也有发现。 我们研究 …

2018年5月1日 · Heritable pulmonary veno-occlusive disease (PVOD) is linked to mutations in the eukaryotic initiation factor 2 alpha kinase 4 (EIF2AK4) gene, leading to a loss of general control nonderepressible 2 (GCN2). The role of GCN2 expression in pulmonary vascular remodeling remains obscure.

Recessive mutations in the EIF2AK4 gene (encoding GCN2) and resultant reduction of GCN2 protein expression are linked to heritable pulmonary veno-occlusive disease (PVOD), a rare subgroup of severe PAH, which is characterized by intimal proliferation and fibrosis of septal veins and preseptal venules .

2021年5月14日 · GCN2 dysfunction led to an enhanced transcription of collagen I gene (col1a1 and col1a2) through decreasing ATF3-dependent p38 phosphorylation inhibition in PVOD, which promotes the collagen I synthesis in pulmonary arterial smooth muscle cells (PASMCs) and eventually leads to increased collagen deposition in pulmonary artery.

GCN2 dysfunction led to an enhanced transcription of collagen I gene (col1a1 and col1a2) through decreasing ATF3-dependent p38 phosphorylation inhibition in PVOD, which promotes the collagen I synthesis in pulmonary arterial smooth muscle cells (PASMCs) and eventually leads to increased collagen deposition in pulmonary artery.

2017年10月1日 · Background Heritable pulmonary veno-occlusive disease (PVOD) is linked to mutations in the EIF2AK4 gene, leading to a loss of GCN2. The role of GCN2-expression in pulmonary vascular...

2024年6月16日 · This consistent pattern of loss or reduction in GCN2 in PVOD, PAH, pulmonary fibrosis, and pulmonary fibrosis-associated pulmonary hypertension strongly suggests a shared pathobiological pathway. In the lung, GCN2 staining is predominantly located in pulmonary artery endothelial cells and, to a lesser extent, in pulmonary artery smooth muscle ...

2022年12月13日 · In this article, Zhou and colleagues show that PVOD-iPSC-ECs exhibited a decrease in GCN2 protein and mRNA expression, when compared to control and GC-ECs. PVOD-ECs exhibited an abnormal endothelial cell phenotype featured by excessive proliferation and angiogenesis, and the malfunctional phenotype was normalized by AZD5363 and MK2206.