The impact of altered haemodynamics on the development of the epicardium

Perdios, Chrysostomos (2019) The impact of altered haemodynamics on the development of the epicardium. PhD thesis, University of Nottingham.

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Abstract

During embryo development the heart is the first functioning organ. Although quiescent in the adult heart, the epicardium is essential during development to form a normal functioning heart. Epicardial derived cells contribute to the heart as it develops, including fibroblasts and vascular smooth muscle cells. Previous studies have shown that a heartbeat is required for epicardium formation. Further, preliminary studies from our laboratory have shown that the development of the epicardium is aberrant when the haemodynamics are altered.

This study aims to investigate how the epicardium and some of its derived cell lineages respond to altered haemodynamics in the developing embryo. Since the aetiology of many congenital heart diseases (CHDs) is unknown, we suggest that an alteration in the heart’s haemodynamics might provide an explanatory basis for some of them. In order to change the heart’s haemodynamics, outflow tract (OFT) banding using a double overhang knot was performed on Hamburger and Hamilton (HH) stage 21 chick embryos, with harvesting at different developmental stages.

Upon alteration of haemodynamics, the epicardium exhibited abnormal morphology and minor bleeding at HH29 using morphological analysis. This phenotype was exacerbated at HH35 with severe changes in the structure of the extracellular matrix (ECM) and the coronary vasculature. A number of genes tied to ECM production were also differentially expressed in HH29 and HH35 OTB hearts including, collagen I and collagen XII. At HH35, there was also downregulation in a number of vascular genes.

It is the first time that the importance of the epicardium is shown regarding CHDs that are caused by altered haemodynamics. In this study, the epicardium was found to be severely impacted by OFT banding. The altered phenotype also showed signs of becoming embryonically lethal as development ensued. More studies should be conducted regarding the effects of haemodynamics on the epicardium with respect to ECM and coronary vessel maturation.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Loughna, Siobhan
Keywords: Epicardium; Epicardium formation; Haemodynamics; Heart development
Subjects: Q Science > QP Physiology
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Life Sciences
Item ID: 56907
Depositing User: Perdios, Chrysostomos
Date Deposited: 21 Oct 2019 07:58
Last Modified: 06 May 2020 13:47
URI: http://eprints.nottingham.ac.uk/id/eprint/56907

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