Interfacing fluid shear stress with vascular oxidative stress: Application of nano and micro sensors

Fluid shear stress is an important factor to consider when studying the behavior of endothelial cells in vascular system. The main focus of this study is to relate the spatial and temporal variations in shear stress with the extent of oxidative stress, specifically in arterial branching points in comparison with straight regions in the vessels. For this purpose, a micro shear stress sensor has been designed and fabricated with the backside wire binding feature. The sensors were flush mounted in a 3-D scaled up model of carotid arterial bifurcation to measure the spatial variations in shear stress. These measurements were validated by computational fluid dynamics simulations. Arteries with complex geometries develop a low profile and bidirectional type of shear stress, namely oscillatory however unidirectional and high profile of shear stress, namely pulsatile shear stress develops at straight regions of the vessels. We compared the extent of oxidative stress for the endothelial cells which were exposed to these types of reconstructed flow profiles.; Reactive oxygen species (ROS), particularly superoxide anion initiate the oxidative modification of low density lipoprotein (LDL) which is one of the fundamental processes to develop plaque formation in cardiovascular disease. NADPH oxidase and mitochondrial respiratory chain are considered as major sources of generation of superoxide. Conversely, nitric oxide is considered atheroprotective and vasodilator. This research has studied the pathways for expression of the enzymes and proteins involved in the generation of free radicals or antioxidants in response to oscillatory and pulsatile shear stress including: subunit NOX4 of NADPH oxidase, eNOS, SOD isoforms, nitrotyrosine, LDL oxidation and nitration using different biochemical techniques. This investigation demonstrated that oscillatory shear stress induced LDL oxidation and nitrotyrosine formation however pulsatile shear stress downregulated both. We studied if 17beta-estradial as a cardioprotective reagent could attenuate the oscillatory shear stress-mediated LDL oxidation. Finally an application of nanotechnology for detection of oxidized LDL is introduced by application of indium oxide nanowire and carbon nanotube based field effect transistors. We observed chemical gating of these transistors upon exposure to oxidized LDL. In conclusion, this interdisciplinary study interfaces fluid shear stress with vascular oxidative stress by application of micro and nano sensors for measurement of shear stress and oxidative modification of LDL.