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.

The influence of anti-TNF therapy on CD31 and VEGF expression in colonic mucosa of Crohn’s disease patients in relation to mucosal healing

“…Vedolizumab interferes with the interaction between gut-selective a4b7-integrin on leukocytes and mucosal addressin cellular adhesion molecule-1 (MadCAM-1) on endothelial cells [15] what down-regulates the migration of leukocytes to the intestinal lamina propria and provides histological improvement [16]. Interestingly, VEGF expression did not correlate in our study group with that of CD31, although VEGF is believed to be one of the most potent pro-angiogenic factors [16][17][18]. In an active inflammatory milieu, however, there is an elevation of concentration of multiple pro-inflammatory cytokines, like TNF-a, interleukin-1 (IL-1), transforming growth factor beta (TGF-a), several other growth factors, and other mediators (like hypoxia inducible factor-1, HIF-1) which indirectly (via VEGF) or directly promote angiogenesis [16].…”

The Nutraceutical Dehydrozingerone and Its Dimer Counteract Inflammation‐ and Oxidative Stress‐Induced Dysfunction of In Vitro Cultured Human Endothelial Cells: A Novel Perspective for the Prevention and Therapy of Atherosclerosis

“…Endothelial dysfunction is considered an initial step in the pathogenesis of atherosclerosis [1, 2]. It is mainly induced by inflammation and oxidative stress leading to structural and functional changes in the vascular endothelium.…”

“…It is mainly induced by inflammation and oxidative stress leading to structural and functional changes in the vascular endothelium. Functional changes of endothelial cells (ECs) include an increase of leukocyte adhesiveness and leukocyte diapedesis [2]. Following activation by inflammatory cytokines such as tumor necrosis factor- (TNF-) α , ECs express chemotactic proteins responsible for leukocyte recruitment [3].…”

Congenital insensitivity to pain and anhydrosis due to a rare mutation and that is complicated by inflammatory bowel disease and amyloidosis: a case report

“…Inflammatory bowel disease is a chronic inflammatory disorder that is comprised of both Crohn's disease and ulcerative colitis. It has a multifactorial etiology that has not been fully elucidated 11. However, inflammatory bowel disease is thought to be the result of a dysregulated immune system in the context of a genetically susceptible individual 12.…”