Ph.D. Dissertation Defense by Ivana Parker
BioEngineering PhD Defense Presentation
March 19, 2015, 3:00 pm
Suddath Room, IBB
Advisor: Manu Platt, Ph.D.
Thesis Committee Members:
Rudy Gleason, Ph.D.
Suzanne Eskin, Ph.D.
W. Robert Taylor, Ph.D.
Roy Sutliff, Ph.D.
Title: The Role of HIV-1 Tat and Antiretrovirals on Cathepsin Mediated Arterial Remodeling
Major advances in highly active antiretroviral therapies (ARVs) have extended the lives of people living with HIV, but there still remains an increased risk of death by cardiovascular diseases (CVD). HIV proteins and ARVs have been shown to contribute to cardiovascular dysfunction with effects on the different cell types that comprise the arterial wall. In particular, HIV-1 transactivating factor, Tat, is a cationic polypeptide that binds to endothelial cells, inducing a range of responses that have been shown to contribute to vascular dysfunction. It is well established that hemodynamics also play an important role in endothelial cell mediated atherosclerotic development where upon exposure to low or oscillatory shear stress, such as that found at branches and bifurcations, endothelial cells contribute to proteolytic vascular remodeling, by upregulating cathepsins, potent elastases and collagenases. Mechanisms to understand the influence of HIV proteins on shear mediated vascular remodeling have not been fully elucidated.
The objective of this thesis is to explore the effects of pro-atherogenic shear stress, HIV proteins, and antiretroviral therapies on the vasculature using in vivo and in vitro models. The goals are to determine the effects of pro-atherogenic shear stress conditions coupled with these HIV factors on proteolytic activity and determine downstream regulatory mechanisms using in vitro culture systems and the HIV-transgenic mouse model.