Inflammation‐driven vascular dysregulation in chronic rhinosinusitis.

Background: Altered neovascularity is typically observed in chronic inflammatory diseases with overlapping pathophysiology to that observed in chronic rhinosinusitis (CRS). However, characterization of these inflammatory‐induced vascular‐mediated changes in CRS is limited. Understanding the underlying vascular changes in CRS will allow for strategic design and development of new drug‐delivery technologies that exploit vascular permeability for increased extravasation into the target sinonasal tissues. Methods: Patients with CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP) and non‐CRS controls were enrolled in this prospective, observational study. The extent of angiogenesis in tissue was characterized using immunohistochemical and multiplex gene expression analyses. Vascular permeability, interendothelial junction structures, and endothelial barrier morphology were evaluated using transmission electron microscopy. Results: Sinonasal vascularity was increased significantly in CRSsNP and CRSwNP (p < 0.05) when compared with controls, as assessed by enumerating the platelet endothelial cell adhesion molecule (PECAM‐1)‒positive blood vessels. Pro‐angiogenic gene expression, including PECAM1 and platelet‐activating factor receptor, was elevated significantly in patients with CRSwNP when compared with controls (p < 0.05). The fenestration sizes between endothelial cells (17‐280 nm) were larger in CRSwNP compared with CRSsNP (10‐33 nm) patients and controls (4‐12 nm). Global thinning of the endothelial cell lining was observed in CRS patients but not in controls. Conclusion: Significant increases in vascularity, the pro‐angiogenic gene, and protein expression and blood vessel morphogenesis were observed in CRS patients compared with controls. In addition, fenestration sizes between interendothelial junction structures were larger in CRS patients than in controls, suggesting inflammation‐driven vascular dysregulation in CRS pathology. [ABSTRACT FROM AUTHOR]