3.2.1 Ferroptosis is involved in the occurrence of AF
Iron overload and oxidative stress are essential pathological processes in ferroptosis. Studies have confirmed that iron overload and oxidative stress affect cardiac pathophysiology and can lead to AF79,80. Nomani et al. found that AF was more common in beta-thalassemia patients than in the normal population, for whom iron overload of the heart and iron-dependent oxidative stress is one of the most important causes of atrial fibrillation81.
Iron overload is related to AF occurrence. It was found that AF was induced by chronic iron overload79. FPN mediates iron efflux, an important protein that regulates iron and calcium homeostasis in cells. After knocking out FPN, rats’ intracellular iron concentration and oxidative stress were further increased, and AF was more likely to be induced12.
Oxidative stress is associated with AF occurrence. In myocardial tissue, elevated ROS levels are associated with AF. Elevated ROS levels lead to protein, lipid, and DNA damage, and are also involved in cardiac structural and electrical remodeling, increasing susceptibility to AF82,83. Connexin distribution and protein level changes were associated with enhanced AF susceptibility84. Studies have found that ROS may induce AF by decreasing the expression of connexin 40 and connexin 4385.
Given the above basis, it has been confirmed that ferroptosis occurs in AF. This study pointed out that cardiac fibroblasts promote the ferroptosis of cardiomyocytes by secreting exosomes, and reduce the loss of cardiomyocytes and oxidative stress damage by interfering with exosome miRNA, which can prevent the continuous development of AF6.