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.