GLP-1 activates KATP channels in coronary pericytes as the effector of brain-gut-heart signalling mediating cardioprotection

TL;DR

GLP-1, a gut hormone, helps protect the heart after a heart attack by relaxing small blood vessels and improving blood flow.

Contribution

The study identifies a brain-gut-heart signaling pathway where GLP-1 activates KATP channels in coronary pericytes to reduce no-reflow after heart attacks.

Findings

GLP-1 activates KATP channels in coronary pericytes to dilate capillaries and reduce no-reflow.

Vagal stimulation and skeletal muscle ischaemia trigger GLP-1 release, which protects the heart.

Blocking KATP channels eliminates the protective effects of GLP-1 on coronary microvasculature.

Abstract

Failure to reperfuse the coronary microvasculature (“no-reflow”) affects up to 50% of patients after unblocking a coronary artery that was causing ischaemia and acute myocardial infarction. This “no-reflow” is associated with reduced left ventricular ejection fraction, increased infarct size and death. We show that the incretin hormone GLP-1 (glucagon-like peptide 1) can be used to protect the heart after ischaemia by activating ATP-sensitive K+ channels on pericytes that constrict coronary capillaries. Coronary capillary dilation can be activated pharmacologically or by vagally-mediated GLP-1 release from the gut evoked by skeletal muscle ischaemia, and is abolished by block or genetic deletion of pericyte KATP channels. These results define a brain-gut-heart pathway mediating cardioprotection and suggest pharmacological therapies to reduce ischaemia-induced coronary no-reflow and improve post-infarct recovery.

After a heart attack, blood flow restoration often fails in small vessels, worsening outcome. Here, the authors show that remote ischaemic preconditioning releases the gut hormone GLP-1, which relaxes cardiac pericytes via KATP channels to reduce capillary constriction and no-reflow.

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