Fig. 2.

Elevated EcSOD abundance/activity prevents extracellular oxidative stress endothelial dysfunction and endothelial cell activation by scavenging superoxide anion. A) EcSOD originating from the skeletal muscle by exercise can be redistributed to nearby myofibers to the myocardium where it removes ROS and prevents myocyte impairment. B) Under normal conditions, NO generated in endothelial cells causes vasodilation in the adjacent smooth muscle cells in arteries. Increased superoxide reacts with nitric oxide (NO), produce peroxynitrite (OONO⁻), which inhibits vasodilation. Exercise-induced increase of EcSOD promotes removal of O₂^.- and preserved NO availability to effectively prevent endothelial dysfunction. C) O₂^.- stimulates pro-inflammatory cytokines and expression of cell surface adhesion molecules, such as VCAM-1, ICAM-1, and E-selectin. Cytokines recruits the leukocytes to interact with endothelial cells through the cell surface adhesion molecules, leading to a vicious cycle of endothelial cell activation as well as leukocyte transendothelial migration, causing tissue damage.