Polo-like kinase 1 promotes pulmonary hypertension

Background Pulmonary hypertension (PH) is a lethal vascular disease with limited therapeutic options. The mechanistic connections between alveolar hypoxia and PH are not well understood. The aim of this study was to investigate the role of mitotic regulator Polo-like kinase 1 (PLK1) in PH development.Methods Mouse lungs along with human pulmonary arterial smooth muscle cells and endothelial cells were used to investigate the effects of hypoxia on PLK1. Hypoxia- or Sugen5416/hypoxia was applied to induce PH in mice. Plk1 heterozygous knockout mice and PLK1 inhibitors (BI 2536 and BI 6727)-treated mice were checked for the significance of PLK1 in the development of PH.Results Hypoxia stimulated PLK1 expression through induction of HIF1a and RELA. Mice with heterozygous deletion of Plk1 were partially resistant to hypoxia-induced PH. PLK1 inhibitors ameliorated PH in mice.Conclusions Augmented PLK1 is essential for the development of PH and is a druggable target for PH.

Automated summary

The study aimed to investigate the role of the mitotic regulator Polo-like kinase 1 (PLK1) in the development of pulmonary hypertension (PH). The results showed that hypoxia stimulated the expression of PLK1 through the induction of HIF1a and RELA. Overexpression of PLK1 was essential for the development of PH, suggesting that PLK1 could be a potential druggable target for PH.