Poor sleep could clog your arteries A mouse study shows how that

first_img C. S. McAlpine, et. al. Nature 10.1038 (2019) Rough sleep is bad for your mind—and your heart. It can increase the risk of clogged arteries, which can lead to stroke or heart attacks. But how these two things are connected has been a mystery. Now, a study in mice reveals a link, based on signals the brain sends to bone marrow. If the story holds true in humans, the mechanism could help explain the connection between sleep and other conditions, from obesity to cancer.  “Not everyone who is sleep-deprived develops cardiovascular disease,” says Namni Goel, a behavioral neuroscientist at the University of Pennsylvania Perelman School of Medicine in Philadelphia who was not involved in the work. The new mouse work “opens the door for human studies” that could sort out who is most at risk.In many forms of cardiovascular disease, fatty deposits build up on artery walls (a condition called atherosclerosis) and can rupture to cause a stroke or heart attack. Immune cells—in particular, white blood cells called monocytes—also play a key role. They flock to sites where these deposits have damaged blood vessels and they spawn cells that can contribute to the growing plaque. To follow up on the known connection between sleep and heart disease, immunologist Filip Swirski of Harvard Medical School and Massachusetts General Hospital in Boston wanted to explore whether sleep somehow triggered an immune process that spurs this dangerous buildup. Email He and his colleagues studied mice that were genetically prone to arterial plaques. To disrupt sleep, they put a mouse in a cage where a metal bar periodically slid across the floor during the 12 daytime hours when mice normally rest. Every 2 minutes, the mouse would feel the nudge of the moving bar and wake up to step over it. While that sounds pretty miserable, Swirski notes that this is one of the least stressful sleep-interrupting techniques the field has dreamed up. (Others have sent mice plunging into water when they nod off.) He thinks of the setup in the experiments as “akin to constantly waking because there’s a little baby in the house.” Poor sleep could clog your arteries. A mouse study shows how that might happen The aortas of mice with interrupted sleep (right image) showed more plaque buildup (red) than those of mice that slept undisturbed. desvitlab/shutterstock.com center_img Sign up for our daily newsletter Get more great content like this delivered right to you! 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Required fields are indicated by an asterisk (*) By Kelly ServickFeb. 13, 2019 , 1:40 PM Compared with sound-sleeping counterparts, mice that underwent 12 weeks of this fragmented sleep had both larger plaques in their arteries and higher levels of two kinds 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 didn’t know what was making those stem cells so active.So the scientists looked to the hypothalamus, a part of the brain involved in regulating wakefulness. A signaling molecule the hypothalamus produces called hypocretin was decreased in the brains of mice with chronically poor sleep. Discovered in 1998 as a stimulator of appetite, hypocretin also promotes wakefulness, and the neurons that make it are deficient in the brains of people with narcolepsy. Swirski’s team found that other mice that were genetically unable to make hypocretin also had more immune cells in their blood, which suggested hypocretin might be an important brake on immune cell production.The researchers then searched mouse bone marrow for cells with a receptor for hypocretin on their surface. The hypocretin-sensitive cells, they discovered, were a subset of white blood cells. And hypocretin appeared to restrict their production of a growth-promoting protein that prompts bone marrow stem cells to make more immune cells. Depleting hypocretin took the brakes off the production of immune cells that would end up in the bloodstream and further clog arteries, the team reports online today in Nature.Why would the body have this kind of brain-bone signaling? Making immune cells costs energy, and in waking hours, an animal needs that energy for other activities, Swirski speculates. So hypocretin, in addition to promoting wakefulness, also tells bone marrow cells, “Hold off—we’re busy with other stuff.” When mice are repeatedly roused, it seems, these hypocretinmaking neurons worked overtime until they got overtaxed.This might not be the only mechanism linking sleep and vascular disease. But it could help explain the increased risk observed in humans, says José Ordovás, a geneticist at Tufts University in Boston whose team recently found that people getting poor or shortened sleep were 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 poor sleep on plaque by injecting the mice with extra hypocretin. Few scientists are ready to suggest based on mouse data alone that dosing people with hypocretin—a molecule with many complicated regulatory roles in the body—would be a good treatment for atherosclerosis. But the study does suggest that a drug that blocks hypocretin receptors—such as the insomnia treatment suvorexant, which the Food and Drug Administration approved in 2014—could raise the risk of cardiovascular disease, two Columbia University physicians, atherosclerosis researcher Alan Tall and sleep specialist Sanja Jelic, write in a commentary to be published alongside the paper.“The connection they’re making is very impressive,” neuroscientist Asya Rolls of the Technion-Israel Institute of Technology in Haifa says of the study. There’s no guarantee that humans have an identical system, and it’s very hard to make comparisons between mouse and human sleep, she notes. But she suspects that the pathway this group uncovered “is affecting much more than atherosclerosis.” For example, previous work has shown that fragmented sleep can boost tumor growth. “Once you start … to affect immunity, you are opening many other conditions that might be explained,” she says.last_img

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