The role of angiopoietins and their mediators in symptomatic gastrointestinal angiodyslasia; novel diagnostic and therapeutic targets in chronic anaemia and obscure gastrointestinal bleeding

Background: Approximately 5% of patients with gastrointestinal bleeding have no source identified on standard endoscopy and are classified as having obscure gastrointestinal bleeding, of which Small Bowel Angiodysplasia (SBA) accounts for more than 50% of cases. Due to limited understanding of the pathophysiology behind SBA no specific treatments are available, and affected patients become dependent on empirical blood transfusions, which are generally suboptimal at correcting their anaemia. This impacts significantly on their quality of life, morbidity and mortality, and places a substantial burden on health care resources. Through research we have already undertaken, we have identified an association between Angiopoietins 1/2 and SBA. These factors could potentially be used as biomarkers and therapeutic targets, which would dramatically improve the outcome for affected patients. Before the association of the Angiopoietins with SBA can be translated into clinical practice we need to further delineate their role in SBA formation. Aims and Methods:
1. To assess the use of Ang1/2 as biomarkers for SBA serum samples will be taken from SBA patients at disease intervals, and from patients with various co-morbidities. ELISA measurements will be performed to determine levels of Ang-1 and Ang-2 and results will be compared.
2. To measure tissue gene expression of the Angiopoietins and other key angiogenic/hypoxic factors in SBA tissue - PCR analysis will be performed to determine gene expression levels of various angiogenic factors in SBA tissue biopsies.
3. To determine the exact location of the Angiopoietins within SBA tissue - Immunohistochemistry will be performed to locate Ang-1, Ang-2 and their receptor within SBA tissue.
4. To measure the response of endothelial cells to alterations in Angiopoietin levels and other hypoxic stimuli - Cell line studies will be performed using HUVECs to determine their response to alterations in levels of Ang-1 and Ang-2 and other factors and hypoxic stimuli.

Award Date
16 May 2014
Award Value
€475,146
Principal Investigator
Dr Grainne Holleran
Host Institution
Trinity College Dublin
Scheme
National SpR/SR Academic Fellowship Programme