A team led by Ludwig Stanford’s Irv Weissman and his Stanford colleague Nicholas Leeper reported in the Proceedings of the National Academy of Sciences in June an intriguing similarity between cancer and atherosclerosis. Their study revealed that an abnormal proliferation of smooth muscle cells that line blood vessels plays a central role in the formation of atherosclerotic plaques. The researchers discovered that in the early stages of plaque formation in a mouse model, a single smooth muscle cell begins to multiply abnormally—an event detectable in human plaques as well. As the descendants of that cell proliferate, they also express high levels of C3, an inflammatory factor associated with atherosclerotic plaques. These proliferating, inflammatory cells would normally be cleared by the immune system’s macrophages but that they also step up their expression of CD47, which transmits a “don’t eat me” signal to macrophages—a tactic employed by cancer cells as well. Knocking down CD47 expression or deleting its gene reduced C3 levels in mice and restored the ability of their macrophages to clear the proliferating cells. This suggests CD47 blockade, which Irv and his team have already developed as a cancer treatment, could also be applied to treat cardiovascular diseases.
This article appeared in the December 2020 issue of Ludwig Link. Click here to download a PDF (1 MB).