Vasogenic bloodborne progenitors and diabetes

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

Diabetes Mellitus (DM) is a group of metabolic disorders which lead to chronic hyperglycaemia. Across all age groups worldwide, the prevalence of DM was recently estimated to be at 2.8% but with an expected rise to 4.4% by the year 2030. Long-term DM carries the significant risk of developing complications, in particular, those which affect the vascular system, such as diabetic nephropathy, neuropathy and retinopathy. Of these, diabetic retinopathy (DR) is the most common, and it remains a leading cause of vision loss in adults between the ages of 20-74.

Underlying these vasodegenerative pathologies is a complex pathogenesis leading to progressive closure of capillaries in the affected organs and results in non-perfusion, attributed to a dysfunction of reparative cells called Endothelial Progenitor Cells (EPCs). EPC is an umbrella term applied to three distinct populations of vasoactive progenitors which contribute to adult (postnatal) angiogenesis in different ways. The circulating EPC can be identified via flow cytometry from peripheral blood mononuclear cells (PBMC5),
and serves as a measure of angiogenic potential. Myeloid Angiogenic Cells (MACs) are pro-angiogenic macrophages. Endothelial Colony Forming Cells (ECFCs) are the de facto endothelial progenitor, contributing directly to vascular repair.

In this PhD project, it was hypothesised that all three classes of EPCs are altered in the context of diabetes. EPCs from patients with diabetes have reduced expression of CD31, suggesting an impairment in angiogenic function. Furthermore, ECFC5 isolated from these patients were also found to show impaired angiogenic function compared to those isolated from non-diabetic controls. MACs isolated from patients with proliferative diabetic retinopathy (PDR) were found to have heterogeneous pro-angiogenic gene expression, suggesting different classes of the condition. Overall, these results show that each player in the angiogenic machinery is altered in some capacity in response to diabetic conditions.
Date of AwardJul 2020
Original languageEnglish
Awarding Institution
  • Queen's University Belfast
SupervisorReinhold Medina (Supervisor), Noemi Lois (Supervisor) & Alan Stitt (Supervisor)

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