Mechanism of IL-6-related spontaneous atrial fibrillation after coronary artery grafting surgery: IL-6 knockout mouse study and human observation

Autor: Haibo Zhao, Malcolm Elliott, Ying Wu, Dianxu Ren, Fangqin Wu, Deng Ying, Liu Yisi, Wei Zhou
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
Cohort Studies
Translational Research
Biomedical
Mice
Postoperative Complications
0302 clinical medicine
Risk Factors
Atrial Fibrillation
Telemetry
Myocyte
Prospective Studies
Coronary Artery Bypass
Mice
Knockout
biology
Models
Cardiovascular
Atrial fibrillation
General Medicine
Middle Aged
Cardiac surgery
medicine.anatomical_structure
030220 oncology & carcinogenesis
Knockout mouse
Inflammation Mediators
medicine.symptom
Artery
STAT3 Transcription Factor
medicine.medical_specialty
Inflammation
03 medical and health sciences
Physiology (medical)
medicine
Animals
Humans
Interleukin 6
Aged
Interleukin-6
business.industry
Biochemistry (medical)
Public Health
Environmental and Occupational Health
Fibroblasts
medicine.disease
Fibrosis
Surgery
Mice
Inbred C57BL
Disease Models
Animal
030104 developmental biology
biology.protein
business
Ex vivo
Zdroj: Translational Research. 233:16-31
ISSN: 1931-5244
DOI: 10.1016/j.trsl.2021.01.007
Popis: Clinical observation and ex vivo studies have established a strong association between inflammation and postoperative atrial fibrillation (POAF). However, it is unclear whether the inflammatory phenotype is causally linked to this event or is an epiphenomenon, and it is not known which inflammatory meditators may increase susceptibility to POAF. The limitations of available animal models of spontaneous POAF (sPOAF) makes it difficult to select an experimental system. Here, we provide experimental and clinical evidence for mechanistic involvement of interleukin-6 (IL-6) in sPOAF. PHASE I: We established a mouse model of cardiac surgery with nonpaced sPOAF. IL-6 knockout mice were protected from sPOAF compared with wild-type mice. PHASE II: At 48 hours after surgery, the heart was separated into 6 regions and cultured. IL-6 was expressed in all regions, with highest abundance in the left atrium (LA). In PHASE III, we demonstrated that IL-6 in the LA elicited early profibrotic properties in atria via the pSTAT3/STAT3 signaling pathway and contributed to sPOAF. PHASE IV: In a translational prospective clinical study, we demonstrated that humans with POAF had a higher IL-6 concentration in pericardial drainage (PD). This study provides preliminary evidence of a causal relationship between IL-6 and POAF in a novel nonpaced sPOAF mouse model. IL-6 is a crucial prerequisite for eliciting profibrotic properties in cardiac myocytes via the pSTAT3 pathway during the early postoperative period, leading to an increased susceptibility to POAF. Measuring IL-6 in PD could be a new noninvasive biomarker for the clinical prediction of POAF.
Databáze: OpenAIRE
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