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

  • Nat Commun. 2026 Feb 14;17(1):2773. doi: 10.1038/s41467-026-69555-1.
Svetlana Mastitskaya  1 ,  Felipe Santos Simões de Freitas  2 ,  Lowri E Evans  3 ,  David Attwell  4
Affiliations
  • 1. Department of Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. [email protected].
  • 2. Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
  • 3. Department of Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
  • 4. Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK. [email protected].
PMID: 41690912 DOI: 10.1038/s41467-026-69555-1
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.

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