Decreased Production of Tissue Plasminogen Activator in Endothelial Cells From Nasal Polyps.

INTRODUCTION

Previous studies have demonstrated that chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by excessive fibrin deposition which is related to impaired production of tissue plasminogen activator(t-PA) by epithelial cells. This study aims to evaluate whether t-PA expression in endothelial cells is also decreased under the inflammatory milieu of CRSwNP.

METHODS

Vascularity and proangiogenic genes expression in polyp tissues from eosinophilic CRSwNP (eCRSwNP) and non-eosinophilic CRSwNP (neCRSwNP) were assessed by immunohistochemistry and real-time PCR. Single-cell RNA sequencing data set of CRS, Immunohistochemistry were used. Human primary nasal endothelial cells were stimulated by IL-13 and IFN-γ with or without retinoic acid.

RESULTS

We observed the increased expression of proangiogenic genes and vascularity in both eCRSwNP and neCRSwNP. Single-cell RNA sequencing and immunostaining revealed that t-PA expression was decreased in endothelial cells of polyp tissues. In vitro study, IL-13 and IFN-γ could significantly attenuate t-PA expression in endothelial cells, which can be rescued by retinoic acid.

CONCLUSIONS

Our findings showed a significant contribution of endothelial cells in the production of t-PA in sinonasal tissues. Furthermore, the levels of t-PA in endothelial cells could also be impaired in the inflammatory environment of CRSwNP. Retinoic acid could restore t-PA expression in endothelial cells impaired by inflammatory cytokines (including IL-13 and IFN- γ), thus degrading the deposited fibrin in polyp tissue.