GLP-1 activates K<sub>ATP</sub> channels in coronary pericytes as the effector of brain-gut-heart signalling mediating cardioprotection.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41690912.
- Also identified by DOI 10.1038/s41467-026-69555-1 and PMC identifier 13018479.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>+</sup> 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 K<sub>ATP</sub> 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.
Medical subject headings
- Pericytes
- KATP Channels
- Glucagon-Like Peptide 1
- Brain