The involvement of CaMKII in myocardial ischaemia-reperfusion injury

Llwyd, Osian 2012. The involvement of CaMKII in myocardial ischaemia-reperfusion injury. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

CaMKII acts as a second messenger to Ca2+ signals within the cardiac myocyte. Cellular stresses such as ischaemia and subsequent reperfusion perturb the normal physiological oscillations of Ca2+ to cause an escalating concentration which damages the cell. CaMKII has been implicated as an injury signal during such cellular conditions. However, there are discrepancies as to whether CaMKII is a possible mechanism of ischaemic preconditioning as its inhibition can abrogate or improve the protective effect of preconditioning. This thesis investigated the effects of CaMKII inhibition in models of ischaemia-reperfusion (I-R) injury. It was hypothesised that CaMKII promotes irreversible injury caused by acute myocardial infarction (AMI), but would also have a beneficial role in mediating cardioprotection by ischaemic preconditioning. This work has demonstrated that: i) in an ex vivo rat heart model of regional I-R injury, CaMKII promoted irreversible injury but is not a feasible target for reperfusion therapy as only a pre-ischaemic intervention reduced myocardial infarction; ii) CaMKII activation was not a pre-requisite for protection with ischaemic preconditioning, although an additive protective effect of CaMKII inhibition and ischaemic preconditioning was possible; iii) models of simulated I-R or oxidative stress in the H9c2 cells did not involve CaMKII activity; iv) isolated cardiac myocytes paced at 1Hz and subjected to simulated I-R do not engage a significant amount of CaMKII activity. These studies substantiate the involvement of CaMKII during ischaemic injury and establish that it does not play a substantial role in ischaemic preconditioning. It highlights the characteristics of the kinase within in vitro models of I-R injury. Understanding CaMKII role in I-R may underpin the development of future therapeutic strategies for the management of AMI.

Item Type:	Thesis (PhD)
Status:	Unpublished
Schools:	Pharmacy
Subjects:	Q Science > Q Science (General)
Uncontrolled Keywords:	CaMKII Ischaemia Reperfusion Preconditioning cardioprotection Heart
Date of First Compliant Deposit:	30 March 2016
Last Modified:	13 Sep 2023 12:16
URI:	https://orca.cardiff.ac.uk/id/eprint/43619

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