Prooxidant Mechanisms in Iron Overload Cardiomyopathy
Figure 3
Involvement of multiple signaling pathways and cardiomyocyte-macrophage interactions in iron overload cardiomyopathy. The schematic diagram showed that iron can enter the cardiomyocytes through both L-type and T-type calcium channels and increased the ROS within cardiac cells. These effects then inhibit the calcium influx, impaired the excitation-contraction coupling and myofilaments contractility, and damage the intracellular organelles, including mitochondria. In addition, iron can activate the TXA2-TP receptor signaling pathway and promote cardiomyocyte-macrophage interaction. With G-CSF supplement, such macrophages recruitment and tissue factor induction will be enhanced, which further increased the ROS and gear up the inflammation-fibrosis circuit, result in aggravation of IOC and cardiac fibrosis.
