Poor sleep can clog your arteries. A study on the mouse shows how this could happen | Science

An agitated sleep is bad for your mind and your heart. This can increase the risk of clogging the arteries, which can lead to a stroke or heart attack. But how these two things are related is a mystery. Now, a study in the mouse reveals a link, based on signals that the brain sends to the bone marrow. If the story is true in humans, the mechanism could help explain the connection between sleep and other conditions, from obesity to cancer.

"All sleep-deprived people do not develop cardiovascular disease," says Namni Goel, neuroscientist of behavior at the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, who did not participate in the work. The new work on mice "opens the door to human studies" that could determine who is most at risk.

In many forms of cardiovascular disease, fatty deposits accumulate on the artery walls (a condition called atherosclerosis) and can rupture to cause a stroke or heart attack. Immune cells, particularly white blood cells called monocytes, also play a key role. They flock to sites where these deposits have damaged blood vessels and generate cells that can contribute to plaque formation. As a follow-up to the known connection between sleep and heart disease, immunologist Filip Swirski of Harvard Medical School and Mbadachusetts General Hospital in Boston investigated whether sleep triggered somehow an immune process to the body. 39, the origin of this dangerous accumulation.

He and his colleagues studied mice genetically predisposed to arterial plaques. To disrupt sleep, they placed a mouse in a cage where a metal bar periodically slid on the floor during the 12 hours of the day the mice were normally resting. Every 2 minutes, the mouse felt the motion of the moving bar and rose to cross it. Although it sounds pretty miserable, Swirski notes that it is one of the least stressful sleep interruption techniques that the field has imagined. (Others sent mice diving into the water when they fell asleep.) He thinks that the configuration of the experiences is like "a constant awakening, because there is a little baby in the house."

Compared to their sleepy counterparts, the mice that experienced this fragmented sleep for 12 weeks had larger plaques in their arteries and higher levels of two types of white blood cells – monocytes and neutrophils – in their blood. The researchers found that these excess immune cells were produced by stem cells in the bone marrow, but they did not know how these stem cells were so active.

Scientists have turned to the hypothalamus, a part of the brain involved in regulating the waking state. A signaling molecule that the hypothalamus produced, called hypocretin, has been diminished in the brains of chronically dormant mice. Discovered in 1998 as an appetite stimulator, hypocretin also promotes wakefulness and its neurons are deficient in the brains of people with narcolepsy. Swirski's team found that other mice that were genetically incapable of making hypocretin also had more immune cells in the blood, suggesting that hypocretin could be a major hindrance to immune cell production. .

The researchers then searched for cells in the bone marrow of mice with a hypocretin receptor on their surface. They discovered that hypocretin-sensitive cells were a subset of white blood cells. And hypocretin seems to limit their production of a growth-promoting protein that causes bone marrow stem cells to produce more immune cells. Impoverishment of hypocretin has slowed the production of immune cells that would end up in the bloodstream and further obstruct the arteries, the team reported today. Nature.

Why would the body have this type of brain-bone signaling? Making immune cells costs energy and, at waking hours, an animal needs this energy for other activities, speculates Swirski. Thus, hypocretin, in addition to promoting wakefulness, also says to bone marrow cells: "Hold on … we are busy with other tasks.

This may not be the only mechanism linking sleep and vascular disease. But this may help explain the increased risk in humans, says José Ordovás, a geneticist at Tufts University in Boston, whose team recently discovered that people who sleep too much or less well are more likely to develop atherosclerosis. even after controlling for risk factors such as obesity. and high blood pressure.

Swirski's team could prevent the effects of lack of sleep on the plate by injecting a mouse hypocretin supplement. Few scientists are willing to suggest, on the sole database of mice, that the administration of a dose of hypocretin, a molecule with multiple complex regulatory functions in the body, would be a good treatment for atherosclerosis. But the study suggests that a drug that blocks hypocretin receptors – such as the treatment of insomnia Suvorexant, approved by the Food and Drug Administration in 2014 – could increase the risk of cardiovascular disease, two Columbia University doctors, researcher Alan Tall and sleep specialist Sanja Jelic, write in a commentary that will be published next to the journal.

"The relationship they have is very impressive," says Asya Rolls, a neuroscientist at the Technion-Israel Institute of Technology in Haifa, about the study. There is no guarantee that humans have an identical system, and it is very difficult to make comparisons between mouse sleep and human sleep, she notes. But she suspects that the pathway uncovered by this group "affects much more than atherosclerosis". For example, previous work has shown that fragmented sleep can stimulate tumor growth. "Once you start … to affect immunity, you open up many other conditions that could be explained," she says.