Department of Systems Biology and Physiology, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States.
Division of Pulmonary Medicine and Critical Care, Cedars-Sinai Medical Center, Los Angeles, California, United States.
Physiology (Bethesda). 2024 Jul 1;39(4):0. doi: 10.1152/physiol.00024.2023. Epub 2024 Mar 19.
Cystic fibrosis (CF) is an inherited disorder caused by a deleterious mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Given that the CFTR protein is a chloride channel expressed on a variety of cells throughout the human body, mutations in this gene impact several organs, particularly the lungs. For this very reason, research regarding CF disease and CFTR function has historically focused on the lung airway epithelium. Nevertheless, it was discovered more than two decades ago that CFTR is also expressed and functional on endothelial cells. Despite the great strides that have been made in understanding the role of CFTR in the airway epithelium, the role of CFTR in the endothelium remains unclear. Considering that the airway epithelium and endothelium work in tandem to allow gas exchange, it becomes very crucial to understand how a defective CFTR protein can impact the pulmonary vasculature and overall lung function. Fortunately, more recent research has been dedicated to elucidating the role of CFTR in the endothelium. As a result, several vascular dysfunctions associated with CF disease have come to light. Here, we summarize the current knowledge on pulmonary vascular dysfunctions in CF and discuss applicable therapies.
囊性纤维化(CF)是一种由囊性纤维化跨膜电导调节因子(CFTR)基因突变引起的遗传性疾病。由于 CFTR 蛋白是一种在人体各种细胞上表达的氯离子通道,因此该基因的突变会影响多个器官,特别是肺部。出于这个原因,关于 CF 疾病和 CFTR 功能的研究历史上一直集中在肺气道上皮上。然而,二十多年前人们发现,CFTR 也在上皮细胞中表达和发挥功能。尽管在理解 CFTR 在气道上皮中的作用方面取得了巨大进展,但 CFTR 在血管内皮中的作用仍不清楚。考虑到气道上皮和内皮细胞协同工作以实现气体交换,了解缺陷型 CFTR 蛋白如何影响肺血管和整体肺功能变得非常重要。幸运的是,最近的研究致力于阐明 CFTR 在血管内皮中的作用。因此,与 CF 疾病相关的几种血管功能障碍已逐渐显现。在这里,我们总结了 CF 中肺血管功能障碍的现有知识,并讨论了适用的治疗方法。