2019 Volume 42 Issue 4 Pages 543-546
Hypertension is one risk for atrial fibrillation (AF) and induces cardiac inflammation. Recent evidence indicates that pressure overload-induced ventricular structural remodeling is associated with the activation of nucleotide binding-oligomerization domain (NOD)-like receptor P3 (NLRP3) inflammasomes, including an apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC). We hypothesized that NLRP3 inflammasomes are an initial sensor for danger signals in pressure overload-induced atrial remodeling, leading to AF. Transverse aortic constriction (TAC) or a sham procedure was performed in mice deficient for ASC−/− and interleukin-1β (IL-1β−/−). One week after the procedure, electrical left atrial burst pacing from the esophagus was performed for 30 s to induce AF. IL-1β, monocyte chemotactic protein 1 (MCP-1), connective tissue growth factor (CTGF), and collagen 1 gene expression were also examined. The electrical burst pacing induced AF in TAC-operated wild-type (WT) (p < 0.001) and ASC−/− (p < 0.05) mice, compared to no AF in the sham-operated WT and ASC−/− mice, respectively. In contrast, the number of mice in which sustained AF was induced was similar between TAC-operated IL-1β−/− and sham-operated IL-1β−/− mice (p > 0.05). The expression of all genes tested was increased in TAC-operated WT and ASC−/− mice compared with sham-operated WT and ASC−/− mouse atria, respectively. CTGF and collagen 1, but not MCP-1, gene expressions were increased in TAC-operated IL-1β−/− mouse atria compared with sham-operated WT and IL-1β−/− mouse atria. In contrast, the IL-1β gene was not detected in either TAC-operated or sham-operated IL-1β−/− mouse atria. These results suggest that an IL-1β activation pathway, different from NLRP3 inflammasomes, plays an important role in pressure overload-induced sustained AF.
