Vascular disease in mice with a dysfunctional circadian clock.
Vascular disease in mice with a dysfunctional circadian clock.
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DOI：
10.1161/circulationaha.108.827477
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发表时间：
2009-03-24
期刊：
影响因子：
37.8
通讯作者：
Rudic RD
中科院分区：
文献类型：
--
作者：
Anea CB;Zhang M;Stepp DW;Simkins GB;Reed G;Fulton DJ;Rudic RD
心血管疾病是美国和世界上男性和女性死亡的主要原因。一天中死亡发生的时间有一个深刻的模式;早晨是内皮细胞最脆弱和血压飙升的时候，中风和心脏病发作最常发生。尽管昼夜节律的分子成分在血管中有节奏地振荡，但缺乏“昼夜节律钟”在血管疾病进展中直接作用的证据。在目前的研究中，我们发现在具有异常昼夜节律的小鼠中，Bmal 1（Bmal 1-KO）和Clock（Clockmut）的病理性重塑和血管损伤增加。此外，来自Bmal 1-KO和Clock突变小鼠的未处理过的小鼠表现出内皮功能障碍。Akt和随后的一氧化氮信号-血管功能的关键途径-显着衰减在动脉Bmal 1-KO小鼠。我们的数据揭示了一个新的作用，生物钟在慢性血管反应，这可能是血管疾病的进展意义。
Cardiovascular disease is the leading cause of death for both men and women in the United States and the world. There is a profound pattern in the time of day at which the death occurs; it is in the morning, when the endothelium is most vulnerable and blood pressure surges, that stroke and heart attack most frequently happen. Though the molecular components of circadian rhythms rhythmically oscillate in blood vessels, evidence of a direct function for the ‘circadian clock’ in the progression to vascular disease is lacking. In the current study, we have found increased pathological remodeling and vascular injury in mice with aberrant circadian rhythms, Bmal1 (Bmal1-KO) and Clock (Clockmut). In addition, naïve aortae from Bmal1-KO and Clock mutant mice exhibit endothelial dysfunction. Akt and subsequent nitric oxide signalling—a pathway critical to vascular function—was significantly attenuated in arteries from Bmal1-KO mice. Our data reveals a new role for the circadian clock during chronic vascular responses which may be of significance in the progression of vascular disease.