Activation of G-protein coupled receptor 55 (GPR55) by endogenous ligand lysophosphatidylinositol (LPI) stimulates numerous pathways, including intracellular calcium release and regulation of gene expression via ERK1/2 MAP kinase activation. The GPR55/LPI system is upregulated in the state of human obesity, as shown by increased adipose tissue mRNA and protein levels of GPR55 alongside elevated plasma concentrations of LPI. Our group has recently shown that exogenous administration of LPI prior to ischaemia/reperfusion (I/R) results in an increased infarct size through GPR55 activation of RhoA-ROCK, therefore we hypothesise that, obese individuals may suffer a worse outcome following myocardial infarction due to GPR55/LPI upregulation.
In the present study, male GPR55-/- and C57Bl/6J mice were fed either a standard chow (SD) or high fat diet (HFD) for 12 weeks, after which mice were anaesthetised and the heart removed and retrogradely perfused using a Langendorff setup. Hearts were stabilised for 15 min followed by 30 min global ischaemia and 30 min reperfusion; hearts were then stained using triphenyltetrazolium chloride to determine infarct size.
Hearts from wild type mice fed a HFD exhibited significantly smaller myocardial infarcts induced by I/R compared to SD fed controls. However, this effect was abrogated in the GPR55-/- mice, suggesting that rather than suffering a worse outcome as hypothesised, endogenous (unlike exogenous) LPI may play a protective role through GPR55. To gain insight into possible mechanisms underlying this protection, studies are currently underway to measure tissue levels of LPI and markers of the RISK pathway activation in infarcted myocardial tissue.
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