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KRIT1 loss-mediated upregulation of NOX1 in stromal cells promotes paracrine pro-angiogenic responses

机译:KRIT1损失介导的基质细胞中NOx1的上调促进了邻静脉促血管生成反应

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摘要

Cerebral cavernous malformation (CCM) is a cerebrovascular disorder of proven genetic origin characterized by abnormally dilated and leaky capillaries occurring mainly in the central nervous system, with a prevalence of 0.3-0.5% in the general population. Genetic studies have identified causative mutations in three genes, CCM1/KRIT1, CCM2 and CCM3, which are involved in the maintenance of vascular homeostasis. However, distinct studies in animal models have clearly shown that CCM gene mutations alone are not sufficient to cause CCM disease, but require additional contributing factors, including stochastic events of increased oxidative stress and inflammation. Consistently, previous studies have shown that up-regulation of NADPH oxidase-mediated production of reactive oxygen species (ROS) in KRIT1 deficient endothelium contributes to the loss of microvessel barrier function.
机译:脑海绵状畸形(CCM)是经过验证的遗传原因的脑血管障碍,其特征在于主要在中枢神经系统中发生异常扩张和漏毛细血管,普遍存在普遍存在的患病率为0.3-0.5%。 遗传研究已经鉴定了三种基因,CCM1 / KRIT1,CCM2和CCM3中的致病突变,其参与维持血管稳态。 然而,在动物模型中的不同研究已经清楚地表明,单独的CCM基因突变不足以引起CCM疾病,而是需要额外的贡献因素,包括增加氧化应激和炎症的随机事件。 始终如一地,先前的研究表明,NADPH氧化酶介导的反应性氧物质(ROS)的上调在KRIT1缺陷的内皮中有助于微血管屏障功能的损失。

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