Impact of reactive oxygen species on biomechanical strength and ECM integrity in the ascending aorta of patients with bicuspid aortic valve (BAV)

Description of projects available to graduate students:
The goal of this work is to elucidate the role of oxidative stress on ECM homeostasis in the ascending aorta. We hypothesize that reduced oxidative stress response mechanisms in aortic SMCs result in accumulation of reactive oxygen species (ROS) that negatively impact the collagen and elastin matrix and biomechanical strength of the BAV aorta. ROS will be quantified and correlated with ultimate tensile and delamination strength of aortic tissue from human patients in: 1) fresh aortic tissue, 2) explant cultures and 3) primary aortic SMC cultures within 3-D fibrin substrates. Parallel experiments will be performed in the presence of selective inhibitors to NADPH and xanthine oxidases and nitric oxide synthase to identify sources of ROS.

Techniques graduate student will learn:
Electron paramagnetic resonance (EPR) spin trapping; immuno spin trapping; biological imaging, including multi-photon microscopy; biomechanical testing; cell culture; mechanical stimulation of 3D fibrin gel constructs within a bioreactor.