VCAM-1 Serves as a Biomarker for Discriminating Eosinophilic CRSwNP and Regulates IL-13-Induced Vascular Remodeling.

Abstract

BackgroundChronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous inflammatory disease with distinct inflammatory endotypes. This study aimed to identify reliable biomarkers for precise discrimination of eosinophilic CRSwNP (eCRSwNP), and to explore their potential roles in the pathological progression of CRSwNP.MethodsA total of 107 patients with CRS (including 22 CRSsNP and 85 CRSwNP) and 40 healthy controls were enrolled. Differentially expressed proteins related to eCRSwNP were screened via protein microarray combined with the random forest algorithm. The expression of candidate proteins was validated in clinical tissues and serum. Correlation analysis and receiver operating characteristic (ROC) curves were applied to evaluate the association of candidate molecules with eosinophilic inflammation and disease prognosis. Hematoxylin and eosin (HE) staining was performed to assess histopathological changes. Human umbilical vein endothelial cells (HUVECs) were used to explore the regulatory effects of IL-13 on VCAM-1 expression and angiogenesis. siRNA knockdown and tube formation assays were further adopted to verify the functional mechanism.ResultsProtein chip and machine learning analysis identified VCAM-1 as a major molecule associated with CRSwNP endotype. VCAM-1 expression was significantly elevated in both tissue and serum of CRSwNP patients, particularly in eosinophil CRSwNP (eCRSwNP) group. HE staining showed a significant increase in neovascularization in the CRSwNP group compared to the control and CRSsNP groups, especially in the eCRSwNP. Multiplex immunofluorescence revealed increased VCAM-1/CD31 co-expression in vascular regions of eCRSwNP tissues. In vitro, IL-13 induced VCAM-1 expression in HUVECs in a time and dose-dependent manner, while VCAM-1 knockdown reduced CD31 levels and impaired angiogenesis, indicating its functional role in pathological neovascularization.ConclusionVCAM-1 is significantly upregulated in eCRSwNP and closely correlated with eosinophilic inflammation. VCAM-1 may facilitate eosinophil infiltration by participating in IL-13-mediated angiogenesis and vascular remodeling in eCRSwNP.