Figure 9.

Diagram showing the possible mechanism of iron overload-induced injury to VECs. Excessive free iron ions produce excess ROS in the cytoplasm. The latter results in biological effects in two ways: excess ROS inhibits DDAHII and accumulates ADMA. ADMA not only inhibits eNOS activity competitively and decreases NO synthesis but also induces eNOS uncoupling and produces even more ROS, thereby cycling and reciprocating ROS, forming one vicious cycle. In addition, excess ROS entered mitochondria, weakening the MMP, opening the mPTP, activating the RIRR mechanism, and forming another vicious circle. These two circles together induce ROS burst, leading to mitochondrial dysfunction, which in turn damages VECs.