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bioRxiv · 10.1101/2025.06.26.661857

Relaxation of cardiac pericytes by GLP-1 activating KATP channels mediates remote ischaemic preconditioning cardioprotection

Mastitskaya, S.·Freitas, F.·Evans, L. E.·Attwell, D.
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Abstract

Failure to reperfuse the coronary microvasculature ("no-reflow") affects up to 50% of patients after unblocking a coronary artery that caused ischaemia and acute myocardial infarction. No-reflow is associated with reduced left ventricular ejection fraction, increased infarct size and death. We have established that no-reflow results from cardiac pericytes constricting coronary capillaries, and that pharmacologically relaxing pericytes reduces no-reflow. Remote ischaemic preconditioning, by briefly making a limb ischaemic, protects against cardiac ischaemic injury, and we have shown this is mediated by release of the gut hormone glucagon-like peptide 1 (GLP-1). We now demonstrate that, by releasing GLP-1, remote ischaemic preconditioning reduces pericyte-mediated coronary capillary constriction and no-reflow, and that the dilating effect of GLP-1 on coronary capillaries is abolished by block or genetic deletion of pericyte KATP channels. These results define a brain-gut-heart pathway mediating remote ischaemic cardioprotection, and suggest pharmacological therapies to reduce ischaemia-induced coronary no-reflow and improve post-infarct recovery.

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Mastitskaya, S., Freitas, F., Evans, L. E., Attwell, D.. 2025-06-30. Relaxation of cardiac pericytes by GLP-1 activating KATP channels mediates remote ischaemic preconditioning cardioprotection. https://doi.org/10.1101/2025.06.26.661857

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