Chen Han, Wang Rui, Xu Fei, Zang Tongtong, Ji Meng, Yin Jiasheng, Chen Jiahui, Shen Li, Ge Junbo
Department of Cardiology, Zhongshan Hospital, Fudan University Shanghai, China.
Shanghai Institute of Cardiovascular Diseases Shanghai, China.
Am J Transl Res. 2020 Sep 15;12(9):5362-5380. eCollection 2020.
Atherosclerosis is a chronic pathological process characterized by the accumulation of inflammation. Overactivation of the sympathetic nervous system accelerates the progression of atherosclerosis. Renal denervation (RDN) reduces the activity of the sympathetic nerve system (SNS) by disrupting sympathetic nerves surrounding renal arteries. We sought to determine whether RDN could mitigate atherosclerosis through the suppression of inflammation. First, we investigated the correlation between plasma norepinephrine concentrations and circulatory inflammation in the progression of atherosclerosis. Then, forty ApoE-/- mice underwent renal denervation or a sham operation after 6 weeks or 12 weeks of feeding with a high-fat diet. The effects of RDN on atherosclerosis in mice were explored. In the development of atherosclerosis, positive correlations were found between SNS activation and the accumulation of circulatory myeloid cells and inflammatory cytokines. In the second part of the study, inhibition of the increase in plaque size was found in both RDN groups compared with that in the sham operation (SO) groups (P<0.05), and RDN also ameliorated inflammation in plaques. Furthermore, RDN attenuated the accumulation of circulating neutrophils and monocytes (P<0.05), which is associated with a significant reduction in levels of several circulating inflammatory cytokines related to hemopoiesis (P<0.05). Flow cytometry analysis revealed comparable levels of neutrophils and monocytes in the bone marrow between all four groups. However, RDN decreased the production and proportions of neutrophils and monocytes in the spleen and reduced splenic sympathetic activity (P<0.05). In summary, our study reveals a novel link between SNS activity and inflammation in atherosclerosis and identifies RDN as a potential anti-inflammatory therapeutic strategy for the treatment of atherosclerosis by restricting the production of splenic immune cells.
动脉粥样硬化是一种以炎症积聚为特征的慢性病理过程。交感神经系统的过度激活会加速动脉粥样硬化的进展。肾去神经支配术（RDN）通过破坏肾动脉周围的交感神经来降低交感神经系统（SNS）的活性。我们试图确定RDN是否可以通过抑制炎症来减轻动脉粥样硬化。首先，我们研究了动脉粥样硬化进展过程中血浆去甲肾上腺素浓度与循环炎症之间的相关性。然后，40只载脂蛋白E基因敲除（ApoE-/-）小鼠在高脂饮食喂养6周或12周后接受肾去神经支配术或假手术。探讨了RDN对小鼠动脉粥样硬化的影响。在动脉粥样硬化的发展过程中，发现SNS激活与循环髓样细胞和炎性细胞因子的积聚之间存在正相关。在研究的第二部分中，与假手术（SO）组相比，两个RDN组均发现斑块大小增加受到抑制（P<0.05），并且RDN还改善了斑块中的炎症。此外，RDN减少了循环中性粒细胞和单核细胞的积聚（P<0.05），这与几种与造血相关的循环炎性细胞因子水平的显著降低有关（P<0.05）。流式细胞术分析显示，所有四组之间骨髓中的中性粒细胞和单核细胞水平相当。然而，RDN降低了脾脏中中性粒细胞和单核细胞的产生和比例，并降低了脾脏交感神经活性（P<0.05）。总之，我们的研究揭示了SNS活性与动脉粥样硬化炎症之间的新联系，并确定RDN是一种潜在的抗炎治疗策略，可通过限制脾脏免疫细胞的产生来治疗动脉粥样硬化。
