The role of HIV-1 tat and antiretrovirals in cathepsin mediated arterial remodeling

HIV;Cardiovascular disease;Arterial remodeling;Cathepsins;antiretroviral therapy;Shear stress;Endothelial cell;Tat

Parker, Ivana Kennedy ; Platt, Manu O. Gleason, Rudolph L. Mechanical Engineering Eskin, Suzanne Taylor, W. Robert Sutliff, Roy ; Platt, Manu O.

University:Georgia Institute of Technology

Department:Mechanical Engineering

关键词: HIV;    Cardiovascular disease;    Arterial remodeling;    Cathepsins;    antiretroviral therapy;    Shear stress;    Endothelial cell;    Tat;   

Others  :  https://smartech.gatech.edu/bitstream/1853/53574/1/PARKER-DISSERTATION-2015.pdf

美国|英语

来源: SMARTech Repository

【 摘 要 】

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. The results of this work demonstrate that upregulation of cathepsins in vivo and in vitro is caused by a synergism between pro-atherogenic shear stress and HIV-1 proteins, elucidates pathways that are activated by HIV-1 Tat and pro-atherogenic shear stress - leading to cathepsin-mediated ECM degradation, and identifies cathepsins as novel biomarkers to monitor the adherence of patients on efavirenz- and tenofovir-containing antiretroviral regimens.