Beyond epithelial damage: vascular and endothelial contributions to idiopathic pulmonary fibrosis.
Beyond epithelial damage: vascular and endothelial contributions to idiopathic pulmonary fibrosis.
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DOI：
10.1172/jci172058
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发表时间：
2023-09-15
影响因子：
15.9
通讯作者：
Jenkins, R. Gisli
中科院分区：
文献类型：
--
作者：
May, James;Mitchell, Jane A.;Jenkins, R. Gisli
特发性肺纤维化（IPF）是一种进行性肺瘢痕形成疾病，生存率低。IPF的发病率和死亡率正在上升，但治疗仍然有限。目前，有两种药物可以减缓疤痕形成过程，但往往以无法忍受的副作用为代价，并且不会显著改变总体生存率。更好地了解IPF的潜在机制可能会改善治疗。目前的范例提出，在遗传致敏个体中，由有害刺激引起的重复性肺泡上皮损伤之后是异常的伤口愈合，包括细胞外基质分泌细胞的异常活性，从而导致组织纤维化和实质损伤。然而，这可能低估了血管对纤维形成的重要性。肺接收100%的心输出量，IPF中的血管异常包括（a）整个纤维化肺的异质血管形成，包括异常扩张血管和血管硬化的发展;（B）内皮细胞（EC）的异常空间分布群体;（c）内皮保护途径如前列环素信号传导的失调;和（d）常见血管和代谢合并症的频率增加。在这里，我们提出血管和EC异常在IPF的病理生物学中既是因果关系又是后果，并且对失调途径的更全面评估可能导致这种毁灭性疾病的有效治疗和治愈。
Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease of the lung with poor survival. The incidence and mortality of IPF are rising, but treatment remains limited. Currently, two drugs can slow the scarring process but often at the expense of intolerable side effects, and without substantially changing overall survival. A better understanding of mechanisms underlying IPF is likely to lead to improved therapies. The current paradigm proposes that repetitive alveolar epithelial injury from noxious stimuli in a genetically primed individual is followed by abnormal wound healing, including aberrant activity of extracellular matrix–secreting cells, with resultant tissue fibrosis and parenchymal damage. However, this may underplay the importance of the vascular contribution to fibrogenesis. The lungs receive 100% of the cardiac output, and vascular abnormalities in IPF include (a) heterogeneous vessel formation throughout fibrotic lung, including the development of abnormal dilated vessels and anastomoses; (b) abnormal spatially distributed populations of endothelial cells (ECs); (c) dysregulation of endothelial protective pathways such as prostacyclin signaling; and (d) an increased frequency of common vascular and metabolic comorbidities. Here, we propose that vascular and EC abnormalities are both causal and consequential in the pathobiology of IPF and that fuller evaluation of dysregulated pathways may lead to effective therapies and a cure for this devastating disease.
影响因子：
5.8
作者：
Pullamsetti S;Krick S;Yilmaz H;Ghofrani HA;Schudt C;Weissmann N;Fuchs B;Seeger W;Grimminger F;Schermuly RT
通讯作者：
Schermuly RT