Getting a good night’s sleep protects against heart disease by controlling production of some immune cells

We all know that we should get a good night’s sleep, but scientists are finding more and more reasons why this is important.

Main finding: The researchers found that broken sleep increases the hardening and narrowing of blood vessels (atherosclerosis). This happens because the brain stops releasing one of its ‘wake up’ chemicals, this tells the bone marrow to make more immune cells and these extra immune cells can go to blood vessels where they contribute to the hardening and narrowing of blood vessels.

Why we care: Lack of sleep has been linked to a range of diseases, but we don’t know much about how sleep (actually lack thereof) increases your risk of getting these diseases. This study unraveled one of the ways in which broken sleep may contribute to cardiovascular disease. The hardening and narrowing of blood vessels (atherosclerosis, which mainly affects large blood vessels, like the aorta) is the leading cause of cardiovascular disease and can lead to blood clots, stroke and heart attacks. So, finding the link between lack of sleep and atherosclerosis could help with the development of drugs to interfere with this sleep- cardiovascular disease connection. Worth noting that this study was all done in mice which had to be sleep interrupted for 12-weeks so it’s not clear yet whether this happens in the same way in people.

How they worked it out:

Step 1: Get mice that are prone to atherosclerosis (vessel hardening and narrowing) and feed them a high fat or high cholesterol diet (yep cholesterol is still a big contributor to heart disease).

Step 2: Deprive some mice of sleep (for 12 weeks) by keeping them in a box with a bar that rolls across the bottom of the box every 2 minutes during mouse sleepy time (day time). Leave other mice in normal boxes so you have a control for your experiment.

Step 3. Do lots of science (more details below).

First, they found that when they did steps 1 and 2, the mice had more atherosclerosis. They work this out because blood vessels with atherosclerosis have clumps (called plaques) in them that narrow the vessel and cause hardening. These clumps are made of lots of things including fats/cholesterol, immune cells, muscle cells and a hole of dead stuff in the middle. So to find atherosclerotic plaques they basically look fatty-immune cell filled clumps on blood vessel walls (just think of this Australian anti-smoking ad).

Anyway point is, mice that have broken sleep have more of these clumps in their blood vessels, they have more immune cells (specifically ones that cause inflammation and go around swallowing up anything they can find — i.e. innate immune cells called monocytes and neutrophils) and they have less of a chemical that your body produces to help keep you awake (hypocretin). But at this stage it is a bit of a chicken and egg situation, you can’t tell what is cause and what is effect, so they did some more science.

To cut a long story (and years of arduous work) short they used lots of different mice: some that couldn’t make the immune cells, some that couldn’t make the awake chemical (hypocretin), mice where they made the awake chemical fluorescent so they could track it, mice where they replaced their immune systems (by bone marrow transplant) and a super creepy experiment where they joined pairs of mice together surgically.

Top Panel: With unbroken sleep the brain produces the awake chemical (hypocretin) which blocks neutrophils in the bone marrow. Bottom Panel: With broken sleep the brain doesn’t produce as much awake chemical so the neutrophils can make the growth protein that promotes production of monocytes. This means there are more monocytea around the body that can eat fat(lipids) and bind to blood vessels this contributing to vessel disease (atherosclerosis). Brain by Meaghan Hendricks from the Noun Project.

End result of all of this was that they found the link between fragmented sleep and cardiovascular disease and here it is: (1) lack of sleep means brain makes less awake chemical (probably to make you go to sleep), this chemical also stops one type of innate immune cell (neutrophil) from producing a protein the promotes generation of other immune cells (2) reduced brain awake chemical means this innate immune cell (neutrophil) makes more of its special innate immune cell making growth protein (CSF-1), (3) More innate immune cell growth protein (CSF-1) means more innate immune cells (specifically monocytes), (4) new immune cells go and get themselves stuck on blood vessel walls and make clumps (i.e. atherosclerosis). Good news is, if you block step 2 or 3 you can stop this from happening, or you could just get some sleep.

Original publication by: McAlpine & friends published in Nature, February 2019

Thanks to Siroon for suggesting this article.

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