Spatial mapping of real-time quantitative shear stress with vascular oxidative stress

Vascular oxidative stress and inflammatory responses are intimately involved in the initiation and progression of atherosclerosis. Hemodynamic forces, specifically, fluid shear stress, play an important role in regulating endothelial cell function. The main focus of the current work is to use different biomedical engineering tools to map the spatial and temporal variations in fluid shear stress with vascular oxidative stress.;Fluid shear stress modulates vascular production of endothelial superoxide anion (O2·) and nitric oxide (·NO). Explants of human coronary arteries were sectioned from the left main bifurcation and RCA for immunohisto-localization of Mn-SOD expression. It was demonstrated that Mn-SOD staining was prominent in relatively straight regions of human coronary arteries. By silencing Mn-SOD, intracellular nitrotyrosine level increased significantly in LDL-treated HAEC. Activation of JNK was uniformly attenuated in the presence of a specific JNK inhibitor. Our findings indicate that PSS and OSS modulate spatial variations in mitochondrial Mn-SOD expression and temporal variations in endothelial mitochondrial O2·-production, suggesting that Mn-SOD plays the important role in protein nitration and activation of JNK represents a mechanism by which shear stress influences mitochondrial redox state.;Based on heat transfer principle, a new generation of biocompatible and flexible intravascular Microelectromechanical Systems (MEMS) sensor was developed to perform real-time hemodynamic assessment. The individual sensor was packaged to the coaxial wire for intravascular deployment in the arterial system of in the aorta of New Zealand White (NZW) rabbits. The sensor was able to detect instantaneous temperature fluctuations of the sensing element in response to changes in blood flow at both high temporal and spatial resolutions. The fluctuations were recorded by a LabVIEW-based data acquisition system as voltage outputs, from which intravascular shear stress (ISS) was inferred. Fluoroscope provided visualization of the location of coaxial wire-based sensors in the rabbit arterial system and ultrasonic imaging provided the blood flow waveform in the abdominal aorta. Computational fluid dynamics (CFD) models of the bifurcation and the straight regions were constructed based on the measured geometry. The non-Newtonian blood properties and the inflow boundary condition acquired from ultrasound measurement were implemented. The simulations were performed with and without the presence of the wire-based sensor to optimize the sensor measurements.;Finally, we developed the heat transfer strategy to assess flow disturbance using the micro-scale sensors. We interfaced MEMS thermal sensors with the high frequency Pulsed Wave (PW) Doppler ultrasound to assess flow reversal in a 3-D stenotic model. Then, we tested our hypothesis that flow disturbance as assessed by the micro-scale sensors in non-obstructive plaques is associated with oxidative stress relevant for initiation of the arterial plaque using a hypercholesterolemic rabbit model. The real-time shear stress was assessed in the healthy/control and atherogenic-prone regions of rabbit aortas. Sensor measurements prior to and after hypercholesterolemic diet were compared. The specific arterial regions were dissected for immunohistochemistry staining. Histopathological analyses demonstrated strong correlation between prominent foam cells in the atherosclerotic lesions and high temporal and spatial variations of shear stress in the aortic arch. Overall, detection and characterization of atherosclerotic lesions are of utmost importance in the management of patients with suspected unstable plaques. The heat transfer strategy established the basis to localize atherogenic hemodynamics; specifically, secondary flow. We believe that simultaneous localization of the non-obstructive plaque and assessment for inflammation hold promise to identify patients at risk for selective intervention.