Scientists from Massachusetts General Hospital (MGH) in Boston, MA, together with colleagues from other research centers, studied the development of atherosclerosis in mice.
Atherosclerosis is the process through which plaques, or fatty deposits, build up inside arteries, causing them to narrow and stiffen. It is a common reason for disease.
The researchers found that sleep-disturbed mice developed larger plaques in their arteries than mice that slept well.
The sleep-disturbed mice also had higher amounts of circulating, inflammatory cells and produced lower amounts of hypocretin, which is a brain hormone that controls wakefulness.
The researchers also saw a reduction in atherosclerosis and inflammatory cells in these mice after they received hypocretin supplementation.
Subject to confirmation in humans, the findings demonstrate that sleep influences cardiovascular health by regulating hypocretin production in the brain.
The journal Nature has recently published a paper about the study.
“We’ve identified a mechanism,” says senior study author Filip K. Swirski, Ph.D., who is an associate professor at MGH and Harvard Medical School, also in Boston, “by which a brain hormone controls production of inflammatory cells in the bone marrow in a way that helps protect the blood vessels from damage.”
Sleep, health, and atherosclerosis
“Sleep is integral to life,” note the authors, and yet insufficient or disturbed sleep is a significant public health issue that affects millions of people.
The Centers for Disease Control and Prevention (CDC) estimate that 35 percent of adults in the United States were regularly sleeping less than 7 hours per 24-hour period in 2014.
Studies have linked lack of sleep to long-term health conditions, such as obesity, type 2 diabetes, depression, and heart disease. However, they have not shed much light on the underlying biological mechanisms.
So, Dr. Swirski and his colleagues decided to investigate how sleep might help to protect cardiovascular health by focusing on the development of atherosclerosis.
The plaques that arise in atherosclerosis can take years to form and consist of calcium, fat molecules, cholesterol, and other substances. As they accumulate, they lessen the flow of nutrient- and oxygen-rich blood.
Atherosclerosis can lead to various other conditions, including coronary heart disease, which develops when plaques build up in the arteries that supply blood to the heart.
Disturbed sleep increased atherosclerosis
Using mice that were genetically predisposed to develop atherosclerosis, the researchers allowed half of them to sleep well and disrupted the sleep of the other half.
Comparing them with the mice that slept well, the team found that the disrupted-sleep mice developed arterial plaques that were up to one third larger.
The sleep-disrupted mice also produced twice the amount of a certain type of inflammatory white blood cell in their bone marrow, and “the lateral hypothalamus” of their brains produced less hypocretin.
Atherosclerosis developed more slowly in sleep-disrupted mice that had hypocretin supplementation compared with those that did not.
The authors note that hypocretin controls blood cell production in bone marrow by regulating CSF1, which is a type of signaling protein.
They conclude that the rise in white blood cells and acceleration of atherosclerosis in the sleep-disturbed mice were due to the reduction of hypocretin and increase in CSF1.
They suggest that undisturbed sleep protects blood vessels from atherosclerotic damage by regulating hypocretin production in the hypothalamus.
The National Heart, Lung, and Blood Institute (NHLBI), which is part of the National Institutes of Health (NIH), funded the research.
Michael Twery, Ph.D., who is director of NHLBI’s National Center on Sleep Disorders Research, says that the study “appears to be the most direct demonstration yet of the molecular connections linking blood and cardiovascular risk factors to sleep health.”
“This anti-inflammatory mechanism is regulated by sleep, and it breaks down when you frequently disrupt sleep or experience poor sleep quality.”
Filip K. Swirski, Ph.D.
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