Endothelial dysfunction in inflammatory bowel diseases: Pathogenesis, assessment and implications

Abstract

Endothelial dysfunction is considered one of the etiological factors of inflammatory bowel disease (IBD). An inflammatory process leads to functional and structural changes in the vascular endothelium. An increase of leukocyte adhesiveness and leukocyte diapedesis, as well as an increased vascular smooth muscle tone and procoagulant activity is observed. Structural changes of the vascular endothelium comprise as well capillary and venule remodeling and proliferation of endothelial cells. Hypoxia in the inflammatory area stimulates angiogenesis by up-regulation of vascular endothelial growth factor, fibroblast growth factor and tumor necrosis factor-α. Inflammatory mediators also alter the lymphatic vessel function and impair lymph flow, exacerbating tissue edema and accumulation of dead cells and bacteria. The endothelial dysfunction might be diagnosed by the use of two main methods: physical and biochemical. Physical methods are based on the assessment of large arteries vasodilatation in response to an increased flow and receptors stimulation. Flow-mediated vasodilatation (FMD) is the method that is the most widely used; however, it is less sensitive in detecting early changes of the endothelium function. Most of the studies demonstrated a decrease of FMD in IBD patients but no changes in the carotic intima-media thickness. Biochemical methods of detecting the endothelial dysfunction are based on the assessment of the synthesis of compounds produced both by the normal and damaged endothelium. The endothelial dysfunction is considered an initial step in the pathogenesis of atherosclerosis in the general population. In IBD patients, the risk of cardiovascular diseases is controversial. Large, prospective studies are needed to establish the role of particular medications or dietary elements in the endothelial dysfunction as well to determine the real risk of cardiovascular diseases.

Keywords: Biomarkers, Cytokines, Diagnosis, Endothelial dysfunction, Inflammatory bowel diseases, Inflammation, Microvasculature

Core tip: Endothelial dysfunction seems to play an important role in the pathogenesis of inflammatory bowel disease (IBD). Inflammatory process leads to functional and structural changes in the vascular endothelium and in consequence its activation. It may contribute to cardiovascular complications, however, in IBD patients, the risk of cardiovascular disease is still controversial. Some of immunomodulatory medications used in IBD treatment may decrease the risk of endothelial dysfunction. In this review article, we present the role of the endothelium in the inflammatory process, diagnostic methods of its dysfunction and current knowledge of the cardiovascular disease risk in IBD.