Effects of flow on reactive oxygen species production in brain versus aortic endothelial cells: The source of ROS generation
Pond, Bethany Leigh
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Endothelial cells are a vital region in the pathophysiology of the vasculature because it is the interface between blood flow and the vessel. One way that the structure of the vessels wall can change is by the accumulation of reactive oxygen species (ROS), which has been correlated to aneurysm formation. Four main ROS sources in endothelial cells are: NADPH oxidase, mitochondria electron transport chain, eNOS uncoupling, and xanthine oxidase. Endothelial cells are an essential component of vasculature that has distinct functions and morphology. The aorta and brain arteries are highly populated by endothelial cells but the morphology and cellular signaling has been shown to be different. This study focuses on the difference between brain and aorta ROS production and how flow affects ROS. Joeseph Moran-Guiati and Jason Kushner provided the brain and aortic endothelial cultures for these studies. NADPH oxidase complex is the main contributor in both cell types but more in brain. Surprisingly, both cell types contain approximately the same number of NOX subunits, suggesting that the difference in ROS production is dependent on how activated these subunits are. Mitochondrial ROS was only significantly generated in brain cells and is verified because brain endothelium contains higher numbers of mitochondria. Both uncoupling of eNOS and xanthine oxidase did not contribute to ROS generation in static cultures. ROS production increased even further in both cell types when cells were exposed to flow and even higher in brain, suggesting that flow effects ROS generation. These results provide useful information in the difference between ROS generation and how it can be harmful in possibly causing intracranial aneurysm formation.