Montefiore Einstein researchers have made an important discovery this past year that could revolutionize the treatment of arterial narrowing caused by atherosclerosis (buildup of cholesterol-rich plaques in artery walls) and/or coronary artery stents. Led by Nicholas Sibinga, MD, Professor of Medicine (Cardiology) and Developmental and Molecular Biology at the Albert Einstein College of Medicine, the study team discovered that a cancer drug (E7386) known to block beta-catenin function effectively disrupted activation of the sphingosine-1-phospate (S1P) pathway — preventing excessive injury response, reducing neointimal thickening after arterial injury, and limiting both atherosclerotic plaque development and necrotic core size using mouse models. 

In the study, published in Science Advances in March 2024, it was found that the vascular injury response is promoted by the interaction of two intracellular signaling mechanisms involved in normal vertebrate development — the Wnt/beta-catenin and S1P signaling pathways. The C-terminus of the beta-catenin protein was found to activate the S1P pathway by targeting expression of the S1P receptor 1 in vascular smooth muscle cells. Both atherosclerosis and the use of stents to open stenosed coronary arteries can trigger an excessive injury response that can narrow arteries even further. A drug that selectively inhibits this vascular repair response could be extremely useful for keeping diseased or damaged arteries open.

This discovery highlights a new potential therapeutic approach to slowing or preventing plaque formation that is distinct from traditional lipid-lowering treatments like statins. By targeting vascular smooth muscle cell signaling and inhibiting the beta-catenin C terminus, this approach could offer a powerful new tool to prevent atherosclerotic plaque buildup and post-stent complications, transforming care for patients with coronary artery disease.