Renal denervation mitigates atherosclerosis in ApoE-/- mice via the suppression of inflammation

Han Chen; Rui Wang; Fei Xu; Tongtong Zang; Meng Ji; Jiasheng Yin; Jiahui Chen; Li Shen; Junbo Ge

Renal denervation mitigates atherosclerosis in ApoE-/- mice via the suppression of inflammation

Am J Transl Res. 2020 Sep 15;12(9):5362-5380. eCollection 2020.

Authors

Han Chen^{1

2}, Rui Wang^{1

2}, Fei Xu^{1

2}, Tongtong Zang^{1

2}, Meng Ji^{1

2}, Jiasheng Yin^{1

2}, Jiahui Chen^{1

2}, Li Shen^{1

2}, Junbo Ge^{1

2}

Affiliations

¹ Department of Cardiology, Zhongshan Hospital, Fudan University Shanghai, China.
² Shanghai Institute of Cardiovascular Diseases Shanghai, China.

PMID: 33042425
PMCID: PMC7540133

Abstract

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.

Keywords: Renal denervation; atherosclerosis; inflammation; sympathetic nerve system.