3.2.2 Different AF risk factors affect AF susceptibility by regulating ferroptosis
Alcohol consumption is one of the common risk factors for AF. A study on the effect of ferroptosis on the susceptibility to AF at different drinking frequencies indicated that frequent excessive drinking would activate ferroptosis and increase the induction rate of AF. Inhibition of ferroptosis could balance the iron overload disorder and reduce the production of reactive oxygen species (ROS), ultimately reducing the susceptibility to AF86. Another study to explore the pharmacological effects of icariin on ethanol-induced atrial remodeling found that excessive ethanol use resulted in severe atrial damage, as indicated by increased susceptibility to AF, altered atrial conduction patterns, enhanced atrial enlargement and fibrosis markers, and up-regulation of ferroptosis related proteins (PTGS2, ACSL4, P53). The expression of anti-ferroptosis-related molecules (GPX4, FTH1) was down-regulated, and these deleterious effects were reversed by treatment with ferrostatin-1 or icariin87.
Obesity is an important risk factor for AF and intestinal microbiota imbalance plays an important role in the pathogenesis of obesity-related AF, which can increase LPS and cause atrial pathological remodeling by activating ferroptosis and inflammasome signaling pathways. Inhibition of ferroptosis or inflammasome signaling significantly ameliorated atrial fibrosis and reduced susceptibility to obesity-related intestinal dysbiosis-induced AF88.
Sepsis is a risk factor for new-onset AF, and ferroptosis is involved in the development of sepsis-induced organ damage. In a recent study, researchers generated an LPS-induced endotoxemia model to understand the mechanism of the link between sepsis-induced ferroptosis and atrial fibrillation. Selective knockdown of Fpn using gene transfection technology was found to increase the intracellular iron concentration and oxidative stress and increase the susceptibility of LPS-induced endotoxemia rats to AF12. (Figure 3)
The above studies have shown that ferroptosis plays an important role in the pathogenesis of atrial fibrillation susceptibility, and intervention of ferroptosis can reduce the susceptibility and progression of AF. However, there is still a lack of relevant research on the specific mechanism of AF and ferroptosis. Clinically, whether the use of ferroptosis inhibitors can reduce the incidence of cardiac stroke and improve the prognosis of some patients who are susceptible to AF or who have already suffered from AF requires further exploration and research by more scholars.