The Vulnerable Vascular Network: Endothelial Dysfunction as a Central Driver of Intestinal Inflammation-A Systematic Review.

Inflammatory bowel diseases (IBDs) encompass Crohn's disease and ulcerative colitis. They represent idiopathic and chronic inflammatory conditions. Mucosal immune dysfunction and compromised gastrointestinal barrier integrity are implicated in the pathophysiological mechanisms of inflammatory bowel diseases. Recent studies have identified endothelial dysfunction as a pivotal mediator in IBD pathogenesis. Through multiple cellular and molecular interactions, endothelial dysfunction orchestrates inflammatory responses. Objectives: This systematic review examines contemporary evidence (2019-2025), emphasising the role of endothelial dysfunction in intestinal inflammation mechanisms, focusing on vascular-epithelial crosstalk, molecular signalling pathways, and therapeutic implications. Methods and results: A comprehensive literature search was conducted using PubMed, Google Scholar, Europe PMC and DOAJ databases, focusing on peer-reviewed articles published between 2019 and 2025. Following the database search and screening process, a total of 53 studies met the eligible criteria and were included in the final analysis. Keywords included "endothelial dysfunction," "inflammatory bowel disease," "gut-vascular barrier," "nitric oxide," and "intestinal inflammation." Contemporary research demonstrates that endothelial dysfunction in IBD manifests through decreased nitric oxide bioavailability, enhanced oxidative stress, aberrant cytokine networks, pathological angiogenesis, and compromised gut-vascular barrier integrity. The emerging concept of dual barrier dysfunction highlights the interdependent relationship between epithelial and endothelial barriers in maintaining intestinal homeostasis. Conclusions: Offering novel therapeutic targets for precision medicine approaches, endothelial dysfunction represents a central driver in the pathophysiological mechanism in IBD. Understanding vascular-epithelial interactions provides fundamental insights for developing targeted interventions to restore intestinal barrier function and resolve chronic inflammation.