Case Control Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Pharmacol Ther. Aug 8, 2020; 11(3): 40-47
Published online Aug 8, 2020. doi: 10.4292/wjgpt.v11.i3.40
Shared changes in angiogenic factors across gastrointestinal vascular conditions: A pilot study
Atiyekeogbebe R Douglas, Grainne Holleran, Sinead M Smith, Deirdre McNamara
Atiyekeogbebe R Douglas, Grainne Holleran, Sinead M Smith, Deirdre McNamara, TAGG Research Centre, School of Medicine, Trinity College Dublin, Dublin D24, Ireland
Author contributions: Douglas AR performed the experiments and wrote the manuscript; Holleran G participated in sample collection; Smith SM served as scientific advisor and was involved in analysis; McNamara D designed the study; corrected the manuscript and served as the guarantor.
Institutional review board statement: Full ethical approval was obtained from the Tallaght Hospital/St James’ Hospital Joint Research Ethics Committee.
Informed consent statement: Written informed consent was obtained from all patients prior to inclusion.
Conflict-of-interest statement: None of the authors had any conflicts of interest to declare.
Data sharing statement: No additional data.
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: Atiyekeogbebe R Douglas, MSc, Research Scientist, TAGG Research Centre, Trinity Centre, Tallaght Hospital, School of Medicine, Trinity College Dublin, College Green, Tallaght, Dublin D24, Ireland. douglaar@tcd.ie
Received: January 4, 2020
Peer-review started: January 14, 2020
First decision: April 8, 2020
Revised: May 11, 2020
Accepted: July 18, 2020
Article in press: July 18, 2020
Published online: August 8, 2020
Processing time: 203 Days and 19.1 Hours
Abstract
BACKGROUND

Neovascularisation is common to a variety of gastrointestinal (GI) disorders with differing aetiologies and presentations; usually affecting adults above 60 years. Shared angiogenic factors modulated by disease specific elements could be a common denominator and represent novel diagnostic and therapeutic targets. As yet, assessment of angiogenic factors across several GI vascular disorders associated with recurrent bleeding and anaemia has not been reported.

AIM

To assess serum levels of angiogenic factors in several intestinal vascular disorders.

METHODS

A case control study was performed in Tallaght University Hospital in patients with endoscopically proven small bowel angiodysplasia (SBA), portal hypertensive gastropathy (PHG), gastric antral vascular ectasia (GAVE) and non-bleeding, non-anaemic controls. Using enzyme-linked immunosorbent assay, concentrations of Angiopoietin 1 (Ang-1), Ang-2 and vascular endothelial growth factor (VEGF) were measured from 2 serum tubes of blood following informed consent. The relative expression of Ang-1 and Ang-2 and Ang-1/2 ratio was calculated and compared between groups. Statistical analysis was applied using a t-test, and a P value of < 0.05 was considered significant.

RESULTS

To date 44 samples were tested: 10 SBA, 11 PHG, 8 GAVE and 15 controls. Mean age 60 (range 20-85) years and 20 (45%) were males. Controls were significantly younger (49 years vs 66 years, P = 0.0005). There was no difference in VEGF levels between the groups (P = 0.6). SBA, PHG and GAVE Ang-1 levels were similar and were significantly lower than controls, (P = 0.0002, 95%CI: 241 to 701). Ang-2 levels were statistically higher in PHG and GAVE groups compared to controls (P = 0.01, 95%CI: 77.8 to 668) and as a result, also had a lower Ang-1/2 ratios compared to controls. While SBA Ang-2 levels were higher than controls, this did not reach statistical significance. Neither age nor haemoglobin level, which was similar between disease groups, could explain the difference. In addition, the median Ang-1/Ang-2 ratio for all patients was found to be significantly lower compared to controls, 8 vs 28 respectively, P = 0.001, 95%CI: -27.55 to -7.12.

CONCLUSION

Our novel pilot study suggests common alterations in Ang-1 and Ang-2 levels across several GI vascular disorders. Differences in Ang-1/Ang-2 ratios among vascular disorders compared to controls suggest disease-specific modulation.

Keywords: Gastric antral vascular ectasia; Portal hypertensive gastropathy; Angiodysplasia; Angiopoietins; Angiogenic factors; Recurrent bleeding

Core tip: This is the first study to look at key angiogenic factors across several distinct intestinal vascular disorders. Our novel study suggests a common alteration in Angiopoietin 1 (Ang-1) levels, a vascular factor associated with vessel stabilization and maturation, across a variety of gastrointestinal vascular disorders. VEGF appears not to play a significant role in these conditions. Serum elevation in Ang-2 levels and lower than normal Ang-1 levels are associated with clinically significant disease and warrant further investigation as potential biomarkers and therapeutic targets. This offers a potential final common pathway which could be of use diagnostically and therapeutically across several vascular conditions.