Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 28, 2021; 27(36): 6142-6153
Published online Sep 28, 2021. doi: 10.3748/wjg.v27.i36.6142
Urotensin II levels in patients with inflammatory bowel disease
Damir Alicic, Dinko Martinovic, Doris Rusic, Piero Marin Zivkovic, Ivana Tadin Hadjina, Marino Vilovic, Marko Kumric, Daria Tokic, Daniela Supe-Domic, Slaven Lupi-Ferandin, Josko Bozic
Damir Alicic, Piero Marin Zivkovic, Ivana Tadin Hadjina, Department of Gastroenterology, University Hospital of Split, Split 21000, Croatia
Dinko Martinovic, Marino Vilovic, Marko Kumric, Josko Bozic, Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
Doris Rusic, Department of Pharmacy, University of Split School of Medicine, Split 21000, Croatia
Daria Tokic, Department of Anesthesiology and Intensive care, University Hospital of Split, Split 21000, Croatia
Daniela Supe-Domic, Department of Health Studies, University of Split, Split 21000, Croatia
Slaven Lupi-Ferandin, Department of Maxillofacial Surgery, University Hospital of Split, Split 21000, Croatia
Author contributions: Bozic J was the guarantor and designed the study; Alicic D, Martinovic D, Rusic D, Zivkovic PM, Tadin Hadjina I, Vilovic M, Kumric M, Tokic D, Lupi-Ferandin S and Supe-Domic D participated in the acquisition, analysis, and interpretation of the data and drafted the initial manuscript; Bozic J, Alicic D and Martinovic D revised the article critically for important intellectual content.
Institutional review board statement: The study was approved by the Ethics Committee of University Hospital of Split, No. 500-03/17-01/86.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: There are no conflict of interest to report.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/
Corresponding author: Josko Bozic, MD, PhD, Associate Professor, Department of Pathophysiology, University of Split School of Medicine, Soltanska 2, Split 21000, Croatia. josko.bozic@mefst.hr
Received: April 27, 2021
Peer-review started: April 27, 2021
First decision: June 13, 2021
Revised: June 17, 2021
Accepted: August 19, 2021
Article in press: August 19, 2021
Published online: September 28, 2021
Abstract
BACKGROUND

Patients with inflammatory bowel disease (IBD) are associated with increased cardiovascular risk and have increased overall cardiovascular burden. On the other hand, urotensin II (UII) is one of the most potent vascular constrictors with immunomodulatory effect that is connected with a number of different cardiometabolic disorders as well. Furthermore, patients with ulcerative colitis have shown increased expression of urotensin II receptor in comparison to healthy controls. Since the features of IBD includes chronic inflammation and endothelial dysfunction as well, it is plausible to assume that there is connection between increased cardiac risk in IBD and UII.

AIM

To determine serum UII levels in patients with IBD and to compare them to control subjects, as well as investigate possible associations with relevant clinical and biochemical parameters.

METHODS

This cross sectional study consecutively enrolled 50 adult IBD patients (26 with Crohn’s disease and 24 with ulcerative colitis) and 50 age and gender matched controls. Clinical assessment was performed by the same experienced gastroenterologist according to the latest guidelines. Ulcerative Colitis Endoscopic Index of Severity and Simple Endoscopic Score for Crohn’s Disease were used for endoscopic evaluation. Serum levels of UII were determined using the enzyme immunoassay kit for human UII, according to the manufacturer’s instructions.

RESULTS

IBD patients have significantly higher concentrations of UII when compared to control subjects (7.57 ± 1.41 vs 1.98 ± 0.69 ng/mL, P < 0.001), while there were no significant differences between Crohn’s disease and ulcerative colitis patients (7.49 ± 1.42 vs 7.65 ± 1.41 ng/mL, P = 0.689). There was a significant positive correlation between serum UII levels and high sensitivity C reactive peptide levels (r = 0.491, P < 0.001) and a significant negative correlation between serum UII levels and total proteins (r = -0.306, P = 0.032). Additionally, there was a significant positive correlation between serum UII levels with both systolic (r = 0.387, P = 0.005) and diastolic (r = 0.352, P = 0.012) blood pressure. Moreover, serum UII levels had a significant positive correlation with Ulcerative Colitis Endoscopic Index of Severity (r = 0.425, P = 0.048) and Simple Endoscopic Score for Crohn’s Disease (r = 0.466, P = 0.028) scores. Multiple linear regression analysis showed that serum UII levels retained significant association with high sensitivity C reactive peptide (β ± standard error, 0.262 ± 0.076, P < 0.001) and systolic blood pressure (0.040 ± 0.017, P = 0.030).

CONCLUSION

It is possible that UII is involved in the complex pathophysiology of cardiovascular complications in IBD patients, and its purpose should be investigated in further studies.

Keywords: Inflammatory bowel disease, Crohn’s disease, Ulcerative colitis, Urotensin II, Cardiovascular risk, Endoscopic activity

Core Tip: Urotensin II (UII) is a potent vasoconstrictor with an immunomodulatory effect that is connected to various cardiovascular disorders. On the other hand, patients with inflammatory bowel disease (IBD) have increased cardiovascular burden as well as increased expression of UII receptors. It is plausible that UII is involved in the complex pathophysiology of IBD complications. In the current study, we investigated UII levels in the IBD population and compared it to matched control subjects, as well as connection of UII with relevant clinical and biochemical parameters. The results of this study showed that serum UII levels are higher in IBD patients in comparison with the control group.