Atherosclerosis is the most common cause of heart attack and stroke. It develops when fats and inflammatory cells are deposited in the vessel wall, forming plaques. A research team involving the DZHK's Munich site (LMU University Hospital Munich) has now identified a mechanism that has received little attention to date: a cannabinoid receptor on the endothelial cells of blood vessels. This receptor facilitates the transport of LDL cholesterol into the vessel wall, thereby promoting atherosclerosis. The study has been published in Nature Communications.
Turbulent blood flow promotes inflammation of the vessels
The endothelium, the inner lining of the blood vessels, plays a central role in the development of atherosclerosis. Where blood vessels branch, blood flow is often uneven. This encourages inflammation in the inner vessel wall. The team was able to show that under these conditions, the cannabinoid receptor CB1 is produced in greater quantities. At the same time, the vessel wall becomes more permeable to LDL cholesterol, which accumulates there and drives plaque formation.
Genetically modified mice lacking the CB1 receptor exclusively in endothelial cells developed significantly fewer atherosclerotic plaques. Their vessel walls were less inflamed and remained denser, allowing less LDL cholesterol to penetrate. The researchers were also able to clarify the underlying mechanism: without CB1, fewer so-called caveolae were formed – small membrane invaginations through which LDL particles are transported through endothelial cells into the vessel wall.
Weight gain slowed
In addition to the effects on the blood vessels, various metabolic parameters also improved. On a high-fat diet, the animals gained less weight, stored less fat in the liver and adipose tissue, and showed better glucose tolerance.
"With our study, we were able to identify a new mechanism by which the cannabinoid receptor CB1 promotes the development of atherosclerosis. This opens up the possibility of specifically blocking CB1 outside the brain in future, thereby protecting the blood vessels," says senior author Prof. Sabine Steffens of the Institute for Cardiovascular Prevention (IPEK) at LMU University Hospital Munich.
CB1 inhibitors that act only outside the brain could, in future, help treat atherosclerosis and related metabolic diseases. However, the findings to date have been obtained solely in cell culture and animal models. Whether this approach also proves effective in humans remains to be shown by future clinical trials.
Background: what cannabinoid receptors do in the body
Cannabinoid receptors were originally discovered because active compounds from the cannabis plant, such as THC and CBD, bind to them. In fact, however, they belong to a signalling system produced by the body itself. They are normally activated by so-called endocannabinoids – messenger substances that the body produces itself, which regulate, among other things, appetite, fat metabolism, inflammatory responses and the function of the blood vessels.
The first CB1 inhibitor, rimonabant, was approved in Europe in 2006 for the treatment of obesity. The drug led to weight loss and improved metabolic values, but it also blocked CB1 receptors in the brain. Owing to an increased risk of depression and other psychiatric side effects, rimonabant was withdrawn from the market again as early as 2008.
The current study therefore pursues a different approach: it investigates peripherally acting CB1 inhibitors that do not reach the brain and act specifically in organs such as the blood vessels, liver and adipose tissue.
Chen B, Prabhu A, Li G, et al. Endothelial cannabinoid CB1 receptor deficiency reduces shear stress-induced arterial inflammation and lipid uptake. Nat Commun. 2026;17(1):5939. doi:10.1038/s41467-026-75214-2
