Yale Cardiovascular Research Center, Department of Internal Medicine and.
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut, USA.
J Clin Invest. 2021 Sep 1;131(17). doi: 10.1172/JCI152716.
Endothelial cells (ECs) under physiologic and pathologic conditions are capable of substantial plasticity that includes the endothelial-mesenchymal transition (EndMT). Notably, in the hypoxic pulmonary circulation EndMT likely drives increases in the pulmonary arterial blood pressure, leading to pulmonary arterial hypertension (PAH). However, it is unclear whether suppressing EndMT can prevent PAH development or mitigate established disease. In this issue of the JCI, Woo et al. generated mice with EC-specific deletion of FGFR1 and -2 and mice with EC-specific expression of a constitutively active FGFR1 to determine the role of FGF signaling in PAH. Mice with FGFR1/2 deletion in ECs that were exposed to hypoxic conditions developed extensive EndMT and more severe PAH than control mice. Animals with the constitutively active endothelial FGFR were protected from hypoxia-induced EndMT and PAH development. These findings suggest that FGF signaling may promote vascular resilience and prevent hypoxia-induced development of EndMT and PAH.
在生理和病理条件下，内皮细胞（ECs）具有很大的可塑性，包括内皮-间充质转化（EndMT）。值得注意的是，在低氧性肺循环中，EndMT 可能导致肺动脉血压升高，从而导致肺动脉高压（PAH）。然而，目前尚不清楚抑制 EndMT 是否可以预防 PAH 的发生或减轻已确诊的疾病。在本期 JCI 中，Woo 等人构建了内皮细胞特异性缺失 FGFR1 和 -2 的小鼠，以及内皮细胞特异性表达组成性激活 FGFR1 的小鼠，以确定 FGF 信号在 PAH 中的作用。在缺氧条件下，内皮细胞中 FGFR1/2 缺失的小鼠发生广泛的 EndMT，并比对照组小鼠发生更严重的 PAH。内皮 FGFR 组成性激活的动物可免受缺氧诱导的 EndMT 和 PAH 发展的影响。这些发现表明，FGF 信号可能促进血管弹性并防止缺氧诱导的 EndMT 和 PAH 的发生。
