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Activin A: expression and potential sources in cardiopulmonary bypass and myocardial ischaemia-reperfusion injury

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thesis
posted on 06.10.2017, 05:44 by Chen, Yi
Activin A, a member of the transforming growth factor-β superfamily of regulatory proteins, has been implicated in both acute and chronic inflammation. Neutralising its biological effects using follistatin, a naturally occurring high affinity binding protein, has been associated with improved outcomes in animal models of inflammatory conditions such as endotoxaemia, inflammatory bowel disease, asthma and renal ischaemia-reperfusion injury. Cardiac surgery is associated with a generalised non- specific inflammatory response and this is largely an effect of cardiopulmonary bypass and myocardial ischaemia-reperfusion injury. In this thesis, the release pattern of activin A and follistatin in the setting of cardiopulmonary bypass and myocardial ischaemia-reperfusion was studied. Cardiopulmonary bypass was associated with a biphasic pattern of activin A release. Follistatin was also robustly released by cardiopulmonary bypass and the serum levels correlated with serum interleukin-6 levels. Activin A expression was increased in myocardial ischaemia-reperfusion and pre-treatment with follistatin reduced infarct size associated with ischaemia-reperfusion. Lastly, neutrophils were identified as a potential source of preformed activin A in acute inflammation. Tumour necrosis factor-α was able to stimulate the release of activin A from neutrophils via a p38 MAP kinase dependent pathway. Overall, this thesis has provided data to support the hypothesis that the activin A/follistatin axis is involved in the inflammatory response to cardiopulmonary bypass and myocardial ischaemia-reperfusion. Circulating neutrophils may be a potential source of preformed activin A in the setting of acute inflammation. Follistatin may have therapeutic potential in ameliorating myocardial ischaemia-reperfusion injury.

History

Principal supervisor

Julian Smith

Year of Award

2013

Department, School or Centre

Department of Surgery (MMC)

Campus location

Australia

Course

Doctor of Philosophy

Degree Type

DOCTORATE

Faculty

Faculty of Medicine Nursing and Health Sciences