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Title: The role of Thymosin Beta 4 in the endogenous epicardial response post-myocardial infarction
Author: Dube, K. N.
ISNI:       0000 0004 5364 9989
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2015
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Advances in pharmacological and interventional strategies for the treatment of ischaemic heart disease and acute myocardial infarction (MI), have paradoxically increased the number of patients living with heart failure. Re-vascularisation of the infarcted myocardium can improve cardiac repair; and thus minimise morbidity and mortality rates in heart failure patients. While a number of re-vascularisation strategies are currently being explored, a major hindrance to successful neovascularisation has been concomitant smooth muscle (SM) support. The epicardium, the epithelial tissue that surrounds the heart, is a developmental source of SM cells (SMCs). Previous work in our lab demonstrated a role for Thymosin Beta 4 (Tβ4) in epicardial activation and systemic SM progenitor differentiation. The aim of this project was to investigate the role of Tβ4 in the endogenous response to MI. I hypothesised that endogenous Tβ4 recapitulates its role during development and activates the adult epicardium post-MI, providing SM support for new vasculature. My data provide evidence that Tβ4 does indeed have a role in the endogenous response post-MI. Tβ4 was found to be upregulated post-MI in the epicardium, and Tβ4 deficiency resulted in a significant reduction in epicardial activation and SM contribution to neovascularisation. A yeast-two-hybrid screen identified Low density lipoprotein receptor-related protein 1 (LRP1) as a potential Tβ4 binding partner. Evidence is further provided of epicardial expression of LRP1 and of its role in epicardial function and neovascularisation during development. Further studies are required to confirm a direct interaction between Tβ4 and LRP1 and to elucidate the precise mechanisms through with the proposed Tβ4-LRP1 interaction may impact epicardial activation and SM differentiation and together contribute to myocardial revascularisation and repair.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available