隨著時間的推移，斑塊會使動脈變硬和變窄。這限製了富氧血液流向心髒和其他器官。動脈粥樣硬化可導致嚴重的問題，包括心髒病發作，中風甚至死亡。
最近的研究將睡眠不足??和某些睡眠障礙（如睡眠呼吸暫停）與心髒病和其他健康狀況的風險增加聯係起來。但是，睡眠與心髒病之間聯係的分子機製尚不清楚。
為了更多地了解睡眠不足對心髒病的影響，由哈佛醫學院和馬薩諸塞州綜合醫院的Filip Swirski博士領導的研究小組研究了一組經基因工程改造以發展動脈粥樣硬化的小鼠。該研究得到NIH國家心肺血液研究所（NHLBI）的部分支持。結果於2019年2月13日在Nature上在線發表。
研究人員反複破壞了一半小鼠的睡眠周期，另一半正常睡眠。 16周後，睡眠中斷的小鼠比正常睡眠模式的小鼠產生更大的動脈斑塊。
睡眠中斷的小鼠在其循環中的某些白細胞水平也比對照小鼠高兩倍。並且它們含有較少量的hypocretin，一種由大腦產生的激素，在調節睡眠和蘇醒狀態（也稱為食欲素）中發揮關鍵作用。進一步的實驗表明，hypocretin抑製了幹細胞的產生，幹細胞在其骨髓中產生白細胞。
接受hypocretin補充的睡眠缺乏小鼠傾向於產生較少的免疫細胞並且發展出比未給予補充的小鼠更小的動脈壁斑塊。這些結果表明，睡眠中斷期間的hypocretin損失導致炎症和動脈粥樣硬化。
Swirski解釋說：“我們已經確定了一種機製，通過這種機製，大腦激素可以控製骨髓炎症細胞的產生，從而有助於保護血管免受損傷。” “這種抗炎機製受到睡眠的調節，當你經常中斷睡眠或睡眠質量不佳時，它就會崩潰。這是一個較大拚圖的一小部分。“
“這似乎是將血液和心血管危險因素與睡眠健康聯係起來的分子聯係的最直接證明，”NHLBI國家睡眠障礙研究中心主任Michael Twery博士說。
如果睡眠中斷被證明對人有類似的影響，這些發現可以為開發治療心髒病的方法開辟新的途徑。
Researchers found that sleep disruption activates a molecule that triggers inflammation and leads to fatty buildup in mouse arteries.
The findings underscore the importance of getting enough quality sleep to maintain heart health. It also suggests new targets for fighting heart disease.
Heart disease is the leading cause of death among women and men in the United States. The most common cause of heart disease is when fatty deposits called plaque build up inside your arteries, the blood vessels that carry oxygen-rich blood around your body. This is called atherosclerosis. White blood cells from the immune system collect at the plaque and cause inflammation.
Over time, the plaque hardens and narrows your arteries. This limits the flow of oxygen-rich blood to your heart and other organs. Atherosclerosis can lead to serious problems, including heart attack, stroke, or even death.
Recent research has linked sleep deficiency and certain sleep disorders, such as sleep apnea, to an increased risk of heart disease and other health conditions. But the molecular mechanisms underlying the link between sleep and heart disease has been unclear.
To learn more about the impact of sleep deficiency on heart disease, a team led by Dr. Filip Swirski at Harvard Medical School and Massachusetts General Hospital studied a group of mice that were genetically engineered to develop atherosclerosis. The research was supported in part by NIH’s National Heart, Lung, and Blood Institute (NHLBI). Results were published online on February 13, 2019, in Nature.
The researchers repeatedly disrupted the sleep cycles of half the mice, and the other half slept normally. After 16 weeks, the sleep-disrupted mice developed larger arterial plaques than the mice with normal sleep patterns.
The sleep-disrupted mice also had twice the level of certain white blood cells in their circulation than the control mice. And they had lower amounts of hypocretin, a hormone made by the brain that plays a key role in regulating sleep and wake states (also known as orexin). Further experiments showed that hypocretin suppressed the production of stem cells that make the white blood cells in their bone marrow.
Sleep-deficient mice that received hypocretin supplementation tended to produce fewer immune cells and develop smaller artery wall plaques than mice that weren’t given the supplementation. These results suggest that hypocretin loss during disrupted sleep contributes to inflammation and atherosclerosis.
“We’ve identified a mechanism 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,” Swirski explains. “This anti-inflammatory mechanism is regulated by sleep, and it breaks down when you frequently disrupt sleep or experience poor sleep quality. It’s a small piece of a larger puzzle.”
“This appears to be the most direct demonstration yet of the molecular connections linking blood and cardiovascular risk factors to sleep health,” says Dr. Michael Twery, director of NHLBI’s National Center on Sleep Disorders Research.
If disrupted sleep proves to have similar effects in people, these findings could open new avenues for developing ways to treat heart disease.
