Researchers have discovered that a protein that protects tumor cells from being attacked by the immune system also has a hand in promoting arterial hardening due to plaque accumulation. As such, limiting the protein may be able to treat atherosclerosis as well, which leads to cardiovascular disease.

Heart attacks and other cardiovascular diseases are usually addressed by targeting risk factors, like high blood pressure and high cholesterol, instead of more direct causes like arterial hardening. Numerous treatments are already in place but none have tackled cardiovascular disease with a focus on the immune system.

The body has a natural way of "taking out the trash," calling on immune system cells known as macrophages to eat up old and dead cells. These cells need to be disposed because they'll release inflammation-causing substances if allowed to remain in the body.

Macrophages determine which cells need disposing by checking for a protein called CD47. All cells have this protein, which sends out "don't eat me" signals to macrophages to show that they are still healthy and functioning. A low amount of CD47 then is the macrophages cue to dispose a certain cell.

Tumor cells also have CD47 but the protein is not depleted on the surface of invasive cells, allowing them to escape the body's cleanup crew. The protein was actually first identified as being overexpressed in cancer cells by Irving Weissman, M.D. and his team.

When the researchers examined atherosclerotic plaques, they discovered that they are filled with old and dead cells. Macrophages should have disposed of those cells but didn't, and it's because the plaques contained extremely high levels of CD47.

Earlier research by Weissman also showed that antibodies can be used to block CD47 activity, restoring the macrophages' ability to dispose of old and dead cells properly.

The researchers used these anti-CD47 antibodies in a simulated atherosclerotic environment and saw that blocking the protein led a decrease in plaque buildup in the arteries, with mice models even showing plaque regression.

Looking at other genetic studies, the researchers learned that high levels of CD47 in arterial plaque correspond to high levels of TNF-alpha, a substance that promotes inflammation. In fact, it's TNF-alpha that's responsible for preventing CD47 from decreasing on old and dead cells. And when old and dead cells release inflammatory substances, more TNF-alpha is also produced.

The researchers are hoping to carry out clinical trials to determine if blocking CD47 can break this vicious cycle.

"This opens up the door for these antibodies' use in noncancerous pathological states where cell proliferation is a primary attribute of the diseased cells," said Weissman.

A patent has been filed for inhibiting CD47 as a way to prevent atherosclerosis.

Photo: Nicolas Raymond | Flickr