研究人员发现,睡眠中断,会激活一种能够引发炎症并导致小鼠动脉脂肪堆积的分子。
研究结果强调了获得足够的优质睡眠以维持心脏健康的重要性。它还提出了抗击心脏病的新目标。
心脏病是美国女性和男性死亡的主要原因。导致心脏病的最常见原因是在动脉内积聚了称为斑块的脂肪沉积物,血管中携带富含氧气的血液。这被称为动脉粥样硬化。来自免疫系统的白细胞聚集在斑块上并引起炎症。
随着时间的推移,斑块会使动脉变硬和变窄。这限制了富氧血液流向心脏和其他器官。动脉粥样硬化可导致严重的问题,包括心脏病发作,中风甚至死亡。
最近的研究将睡眠不足??和某些睡眠障碍(如睡眠呼吸暂停)与心脏病和其他健康状况的风险增加联系起来。但是,睡眠与心脏病之间联系的分子机制尚不清楚。
为了更多地了解睡眠不足对心脏病的影响,由哈佛医学院和马萨诸塞州综合医院的Filip Swirski博士领导的研究小组研究了一组经基因工程改造以发展动脉粥样硬化的小鼠。该研究得到NIH国家心肺血液研究所(NHLBI)的部分支持。结果于2019年2月13日在Nature上在线发表。
研究人员反复破坏了一半小鼠的睡眠周期,另一半正常睡眠。 16周后,睡眠中断的小鼠比正常睡眠模式的小鼠产生更大的动脉斑块。
睡眠中断的小鼠在其循环中的某些白细胞水平也比对照小鼠高两倍。并且它们含有较少量的hypocretin,一种由大脑产生的激素,在调节睡眠和苏醒状态(也称为食欲素)中发挥关键作用。进一步的实验表明,hypocretin抑制了干细胞的产生,干细胞在其骨髓中产生白细胞。
接受hypocretin补充的睡眠缺乏小鼠倾向于产生较少的免疫细胞并且发展出比未给予补充的小鼠更小的动脉壁斑块。这些结果表明,睡眠中断期间的hypocretin损失导致炎症和动脉粥样硬化。
Swirski解释说:“我们已经确定了一种机制,通过这种机制,大脑激素可以控制骨髓炎症细胞的产生,从而有助于保护血管免受损伤。” “这种抗炎机制受到睡眠的调节,当你经常中断睡眠或睡眠质量不佳时,它就会崩溃。这是一个较大拼图的一小部分。“
“这似乎是将血液和心血管危险因素与睡眠健康联系起来的分子联系的最直接证明,”NHLBI国家睡眠障碍研究中心主任Michael Twery博士说。
如果睡眠中断被证明对人有类似的影响,这些发现可以为开发治疗心脏病的方法开辟新的途径。
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.