Since GLP-1 blockbusters semaglutide and tirzepatide broke into the mainstream for their ability to treat diabetes and provoke weight loss, evidence has been piling up that the molecules can reduce the risk of heart problems too. New data from rats and mice demonstrate that GLP-1s can support heart attack recovery by helping blood vessels relax—literally.
When coronary arteries—which funnel blood to the heart—fill with plaque, they can become clogged and cause a heart attack. After the plaque is plunged from the system, blood vessels can remain squeezed too tight in a state known as “no-reflow,” causing further complications even after the immediate emergency has passed.
Giving GLP-1 mimic exendin-4 to rodents with constricted blood vessels caused their capillaries to relax back to a normal state, researchers reported in Nature Communications on March 2.
The results suggest that existing GLP-1 drugs, like Novo Nordisk’s semaglutide and Eli Lilly’s tirzepatide, could be “repurposed to treat the risk of ‘no-reflow’ in heart attack patients, offering a potentially life-saving solution,” David Attwell, Ph.D., a neuroscientist at University College London and one of the leaders of the new study, said in a related release.
The researchers sought to understand why blocked bloodflow in other parts of the body, like the limbs, can help prevent heart attacks later on, a phenomenon known as remote ischemic preconditioning.
They determined that when the brain detects blocked bloodflow it triggers the release of GLP-1 molecules from the gut, which then binds to receptors on the surface of cells called pericytes. Pericytes form part of the blood vessel architecture, and by activating their potassium transport mechanism, the GLP-1s induce the pericytes to relax.
The pathway, therefore, represents a connection between the brain, gut and heart, the authors noted. The nervous system’s role in heart attacks has become increasingly recognized, with another recent paper finding that the common killer is caused more by neurons gone haywire than by clogged arteries.
Semaglutide and tirzepatide have a proven ability to reduce the risk of heart-related deaths in patients with obesity and Type 2 diabetes. Semaglutide is approved for the reduction of cardiovascular risk in these two patient populations, while Lilly is seeking similar approval for tirzepatide.