Sleep is vital to good health for a variety of reasons. Studies have shown, for example, that the risk of heart disease increases when people don’t get enough sleep. Researchers at Massachusetts General Hospital (MGH) have now found one reason why. Insufficient sleep promotes the production of specific white blood cells, and those inflammatory cells contribute to the buildup of plaque in the arteries - also known as atherosclerosis. The findings have been reported in Nature.
“We have discovered that sleep helps to regulate the production in the bone marrow of inflammatory cells and the health of blood vessels and that, conversely, sleep disruption breaks down control of inflammatory cell production, leading to more inflammation and more heart disease,” explained the senior author of the study Filip Swirski, Ph.D., of the MGH Center for Systems Biology.
"We also have identified how a hormone in the brain known to control wakefulness controls processes in the bone marrow and protects against cardiovascular disease," he added.
In this work, the researchers used a mouse model of atherosclerosis. Those mice were then subjected to repeated sleep interruptions meant to mimic disrupted human sleep. The mice did not experience changes in glucose tolerance, cholesterol or weight compared to atherosclerotic mice with uninterrupted sleep. But they did end up with larger plaques in their arteries and higher levels of white blood cells called monocytes and neutrophils. Those cell types are known to contribute to the development of atherosclerosis.
Additional work indicated that in sleep-deprived mice, the production of bone marrow, which generates white blood cells, was ramped up nearly twofold. Levels of a hormone called hypocretin were also significantly reduced in mice that had been deprived of sleep. That hormone is made in the brain by the hypothalamus and helps regulate sleep. The researchers were surprised to find that it also plays a part in the production of white blood cells.
The researchers learned that in bone marrow, hypocretin interacts with cells that give rise to neutrophils. Research using mice engineered to lack the hormone showed that hypocretin controls the expression of a molecule called CSF-1, the production of monocytes, and arterial plaque development. When hypocretin levels drop, neutrophils make more CSF-1, monocyte production increases and atherosclerosis is accelerated.
“This is a direct demonstration that hypocretin is also an important inflammatory mediator,” noted Swirski, who is an associate professor of Radiology at Harvard Medical School. “We now need to study this pathway in humans, explore additional mechanisms by which proper sleep maintains vascular health and further explore this newly identified neuro-immune axis.”