Inhibition of the P2X7 receptor prevents atrial proarrhythmic remodeling in experimental post-operative atrial fibrillation.
Int Immunopharmacol
; 129: 111536, 2024 Mar 10.
Article
en En
| MEDLINE
| ID: mdl-38320354
ABSTRACT
BACKGROUND:
Post-operative atrial fibrillation (POAF) is a common complication in patients undergoing cardiac surgery. The purinergic receptor P2X7 (P2X7R) is involved in some cardiovascular diseases, whereas its effects on atrial fibrillation (AF) are unclear.OBJECTIVE:
This study was to assess the effect of P2X7R on atrial arrhythmogenic remodeling in the rat model of sterile pericarditis (SP).METHODS:
Male Sprague-Dawley (SD) rats were used to induce the SP model. Electrocardiogram, atrial electrophysiological protocol, histology, mRNA sequencing, real-time quantitative PCR, western blot, and Elisa assay were performed.RESULTS:
SP significantly up-regulated P2X7R expression; increased AF susceptibility; reduced the protein expression of ion channels including Nav1.5, Cav1.2, Kv4.2, Kv4.3, and Kv1.5; caused atrial fibrosis; increased norepinephrine (NE) level in plasma; promoted the production of inflammatory cytokines such as TNF-α, IL-1ß, and IL-6; increased the accumulation of immune cells (CD68- and MPO- positive cells); and activated NLRP3 inflammasome signaling pathway. P2X7R antagonist Brilliant Blue G (BBG) mitigated SP-induced alterations. The mRNA sequencing demonstrated that BBG prevented POAF mainly by regulating the immune system. In addition, another selective P2X7R antagonist A740003, and IL-1R antagonist anakinra also reduced AF inducibility in the SP model.CONCLUSIONS:
P2X7R inhibition prevents SP-induced atrial proarrhythmic remodeling, which is closely associated with the improvement of inflammatory changes, ion channel expression, atrial fibrosis, and sympathetic activation. The findings point to P2X7R inhibition as a promising target for AF (particularly POAF) and perhaps other conditions.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Pericarditis
/
Fibrilación Atrial
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
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Male
Idioma:
En
Revista:
Int Immunopharmacol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
FARMACOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China