Renal sympathetic denervation ameliorates the activated inflammatory response through JAK-STAT pathway in a chronic obstructive sleep apnea animal model

Ya-Wen Hsiao; Wei-Lun Lin; Yu-Hui Chou; Shin-Huei Liu; Ting-Wei Ernie Liao; Shih-Ann Chen; Li-Wei Lo

doi:10.1016/j.sleep.2023.11.028

Renal sympathetic denervation ameliorates the activated inflammatory response through JAK-STAT pathway in a chronic obstructive sleep apnea animal model

Sleep Med. 2024 Jan:113:142-151. doi: 10.1016/j.sleep.2023.11.028. Epub 2023 Nov 21.

Authors

Ya-Wen Hsiao¹, Wei-Lun Lin², Yu-Hui Chou³, Shin-Huei Liu⁴, Ting-Wei Ernie Liao⁴, Shih-Ann Chen⁵, Li-Wei Lo⁶

Affiliations

¹ Division of Holistic and Multidisciplinary Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
² Institute of Clinical Medicine, and Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan; Institute of Biomedical Sciences, MacKay Medical College, New Taipei City, Taiwan; Taichung Veterans General Hospital Taichung, Taiwan.
³ Institute of Clinical Medicine, and Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan; Taichung Veterans General Hospital Taichung, Taiwan.
⁴ Division of Holistic and Multidisciplinary Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, and Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan; Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
⁵ Division of Holistic and Multidisciplinary Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, and Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan; Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Taichung Veterans General Hospital Taichung, Taiwan; National Chung Hsing University, Taichung, Taiwan. Electronic address: [email protected].
⁶ Division of Holistic and Multidisciplinary Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, and Cardiovascular Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan; Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. Electronic address: [email protected].

PMID: 38016360
DOI: 10.1016/j.sleep.2023.11.028

Abstract

Objectives: Obstructive sleep apnea (OSA) is known to increase the risk of cardiovascular disease and inflammation plays a significant role in this process. Renal denervation (RDN) is a novel approach aimed at reducing sympathetic nervous system activity. The role of RDN in the inflammatory response to chronic OSA (COSA) is currently unclear. The main objective was to study inflammatory mechanisms in the rabbit heart with COSA and the effects of RDN.

Methods: Eighteen rabbits were randomized into three groups: sham control, COSA, and COSA-RDN. COSA and COSA-RDN groups received liquid silicone injections, while the sham control group received normal saline. We performed combined surgical and chemical RDN through bilateral retroperitoneal flank incisions in the COSA-RDN group after silicone injections. The inflammatory mechanisms were assessed through immunoblotting, real-time PCR, and ELISA after the experiment.

Results: H&E staining showed immune cell infiltration in COSA, which decreased after RDN treatment. The level of α7nAChR was significantly reduced in COSA compared to the sham control but was restored to a similar level in the COSA-RDN group. Furthermore, the expressions of p-JAK2 and p-STAT3 were significantly reduced in COSA but showed an up-regulation following RDN treatment. Similarly, levels of the inflammatory markers IL-6, IL-1β and TNF-α were markedly increased in COSA but decreased after RDN therapy. We observed NF-κB activation in the COSA rabbit model, which decreased after RDN treatment, as evidenced by decreased NF-κB expression.

Conclusions: Our study suggests that RDN treatment may prevent COSA-associated heart inflammation via the JAK2-STAT3 signaling pathway.

MeSH terms

Animals
Disease Models, Animal
Inflammation
Janus Kinases*
NF-kappa B
Rabbits
STAT Transcription Factors
Signal Transduction
Silicones
Sleep Apnea, Obstructive* / surgery
Sympathectomy

Substances

Janus Kinases
NF-kappa B
STAT Transcription Factors
Silicones