From the Department of Stomatology (M.X., Q.T., J.N., X.Z., S.Y., J.S., L.C.), Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China (M.X., Q.T., J.N., X.Z., S.Y., J.S., L.C.).
Circ Res. 2020 Mar 13;126(6):e15-e29. doi: 10.1161/CIRCRESAHA.119.315502. Epub 2020 Feb 11.
Atherosclerotic cardiovascular diseases are the leading cause of mortality worldwide. Atherosclerotic cardiovascular diseases are considered as chronic inflammation processes. In addition to risk factors associated with the cardiovascular system itself, pathogenic bacteria such as the periodontitis-associated () are also closely correlated with the development of atherosclerosis, but the underlying mechanisms are still elusive.
To elucidate the mechanisms of -accelerated atherosclerosis and explore novel therapeutic strategies of atherosclerotic cardiovascular diseases.
(brain and muscle Arnt-like protein 1) mice, mice, mice, conditional endothelial cell knockout mice (; -Cre mice), and the corresponding jet-legged mouse model were used. accelerates atherosclerosis progression by triggering arterial oxidative stress and inflammatory responses in mice, accompanied by the perturbed circadian clock. Circadian clock disruption boosts -induced atherosclerosis progression. The mechanistic dissection shows that infection activates the TLRs-NF-κB signaling axis, which subsequently recruits DNMT-1 to methylate the promoter and thus suppresses transcription. The downregulation of BMAL1 releases CLOCK, which phosphorylates p65 and further enhances NF-κB signaling, elevating oxidative stress and inflammatory response in human aortic endothelial cells. Besides, the mouse model exhibits that joint administration of metronidazole and melatonin serves as an effective strategy for treating atherosclerotic cardiovascular diseases.
accelerates atherosclerosis via the NF-κB-BMAL1-NF-κB signaling loop. Melatonin and metronidazole are promising auxiliary medications toward atherosclerotic cardiovascular diseases.
动脉粥样硬化性心血管疾病是全球范围内导致死亡的主要原因。动脉粥样硬化性心血管疾病被认为是慢性炎症过程。除了与心血管系统本身相关的危险因素外，牙周炎相关的致病细菌（）也与动脉粥样硬化的发展密切相关，但潜在机制仍不清楚。
阐明 - 加速动脉粥样硬化的机制，并探索动脉粥样硬化性心血管疾病的新治疗策略。
使用（脑和肌肉芳香烃受体核转录因子样蛋白 1）小鼠、 小鼠、 小鼠、条件性内皮细胞 敲除小鼠（；-Cre 小鼠）和相应的jet-legged 小鼠模型。 在 小鼠中通过触发动脉氧化应激和炎症反应来加速动脉粥样硬化的进展，同时扰乱了昼夜节律。昼夜节律紊乱会加剧 - 诱导的动脉粥样硬化进展。机制剖析表明， 感染激活 TLRs-NF-κB 信号轴，随后招募 DNMT-1 甲基化 启动子，从而抑制 转录。BMAL1 的下调释放 CLOCK，其磷酸化 p65 并进一步增强 NF-κB 信号，增加人主动脉内皮细胞中的氧化应激和炎症反应。此外，该小鼠模型表明，联合使用甲硝唑和褪黑素是治疗动脉粥样硬化性心血管疾病的有效策略。
通过 NF-κB-BMAL1-NF-κB 信号环加速动脉粥样硬化。褪黑素和甲硝唑是治疗动脉粥样硬化性心血管疾病有前途的辅助药物。
