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Role of cyclophilins and heat shock proteins in myocardial ischaemia/reperfusion injury.

Folarin, N'deen; (2004) Role of cyclophilins and heat shock proteins in myocardial ischaemia/reperfusion injury. Doctoral thesis , University of London. Green open access

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Abstract

Restoration of blood flow after myocardial infarction (MI), surgery or fibrinolytic therapy is necessary, but can lead to cardiomyocyte dysfunction within a generalised condition commonly known as "reperfusion injury". The role of cyclophilins, heat shock proteins (HSP), and the mitochondrial chaperone complex (MCC), was studied in this pathological condition. In vitro and in vivo models were used to replicate conditions of ischaemia/reperfusion (IR) injury. H9c2 and COS-7 cell lines were employed in nitric oxide (NO) donor and transfection applications. Experimental protocols were used to determine mitochondrial membrane potential (MMP), mitochondrial morphology, protein expression, enzyme activity and cell damage in these models. No difference was observed in activity or expression in cyclophilin or expression of the MCC in any of the models. It was noted that in the in vitro model, cell death was predominantly necrotic with only a minority of cells undergoing apoptosis, and as the degree of ischaemia increased cell death was 100% necrotic. The NO donor afforded protection against lethal ischaemia in H9c2 cells, but there was no detectable increase in expression of any HSP's. Transfection of cyclophilin-D (CyP-D, CyP3) into COS-7 cell lines demonstrated no changes in any tested parameters. Both subsarcolemmal (SSM) and interfibrillar (IFM) MMP decreased in all experimental groups, which were reperfused after ischaemia. More importantly SSM MMP decreased to a greater extent than IFM MMP, therefore demonstrating a greater sensitization to IR.

Type: Thesis (Doctoral)
Title: Role of cyclophilins and heat shock proteins in myocardial ischaemia/reperfusion injury.
Identifier: PQ ETD:602754
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by Proquest
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Surgical Biotechnology
URI: http://discovery.ucl.ac.uk/id/eprint/1446812
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