Oxidative Stress Contributes to Endothelial Dysfunction in Mouse Models of Hereditary Hemorrhagic Telangiectasia
Figure 5
Model of oxidative stress in mutant mice leading to vascular endothelial damage. In Eng +/− and Alk1 +/− mice, altered eNOS activation renders the enzyme refractory to regulation by TGF-β/BMP signaling and represents a critical event leading to excessive oxidative stress. Uncoupled eNOS produces low amounts of NO and high levels of oxygen radicals (). The NOS inhibitor, L-NAME, inhibits ROS production in tissues of mutant mice. Superoxide dismutase (SOD) and the SOD mimetic compound Tempol convert into less harmful hydrogen peroxide (H2O2). A large portion of ROS is produced by mitochondria (Antimycin-inhibitable) and NADPH oxidases (Apocynin-inhibitable) however that percentage does not differ between mutant and control mice. Low NO cellular level may also inhibit mitochondrial KATP channel (mitoKATP) opening, trigger permeability transition pores (PTP) opening, and further increase the oxidative stress caused by mitochondrial ROS release.
