Prooxidant Mechanisms in Iron Overload Cardiomyopathy
Figure 1
TXA2 mediates iron overload cardiomyopathy through TNF-α associated calcineurin-NFAT signaling pathway. The schematic diagram depicted that iron loading can activate TXA2 and induces TNF-α production in which can be inhibited by NFAT-SiRNA, calcineurin inhibitor (CsA), or calcium chelator (BAPTA). Addition of TXA2 agonist, U46619, can facilitate nuclear translocation of NFAT, thus increase proinflammatory marker TNF-α expression. These findings demonstrate a novel molecular mechanism of TXA2 in mediating iron overdosed cardiomyopathy and the involvement of calcineurin-NFAT signaling cascades in cardiac chronic inflammation.
