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World J Gastroenterol. Jan 21, 2016; 22(3): 1067-1077
Published online Jan 21, 2016. doi: 10.3748/wjg.v22.i3.1067
Endothelial dysfunction in inflammatory bowel diseases: Pathogenesis, assessment and implications
Dorota Cibor, Renata Domagala-Rodacka, Tomasz Rodacki, Artur Jurczyszyn, Tomasz Mach, Danuta Owczarek
Dorota Cibor, Tomasz Mach, Danuta Owczarek, Department of Gastroenterology, Hepatology and Infectious Diseases, Jagiellonian University Medical College, 31-531 Cracow, Poland
Renata Domagala-Rodacka, Master of Pharmacy, 31-531 Cracow, Poland
Tomasz Rodacki, Department of Food Chemistry and Nutrition, Jagiellonian University Medical College, 30-688 Cracow, Poland
Artur Jurczyszyn, Department of Hematology, Jagiellonian University Medical College, 31-531 Cracow, Poland
Author contributions: Cibor D designed the paper, searched and analyzed literature, drafted and revised the paper, approved the final version; Domagala-Rodacka R and Rodacki T performed tables and figures, drafted and revised the paper, approved the final version; Jurczyszyn A, Mach T and Owczarek D searched and analyzed literature, drafted and the revised paper, approved the final version.
Conflict-of-interest statement: The authors do not declare any conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dorota Cibor, MD, PhD, Department of Gastroenterology, Hepatology and Infectious Diseases, Jagiellonian University Medical College, Sniadeckich 5 Str, 31-531 Cracow, Poland. dorota.cibor@gmail.com
Telephone: +48-12-4247340 Fax: +48-12-4247380
Received: April 29, 2015
Peer-review started: May 12, 2015
First decision: July 20, 2015
Revised: August 24, 2015
Accepted: November 30, 2015
Article in press: November 30, 2015
Published online: January 21, 2016
Processing time: 261 Days and 10.1 Hours
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.