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.