103 - The Effects of the Tat86 and Tat101 Isoforms on Oxidative Stress in Human Pulmonary Artery Endothelial Cells: Potential Role in HIV-Associated Pulmonary Arterial Hypertension

Abstract

Occlusive arterial remodeling driven by hyperproliferation of endothelial and smooth muscle cells is characteristic of pulmonary arterial hypertension (PAH) and known to be driven by pulmonary vascular inflammation and oxidative stress. Human immunodeficiency virus (HIV) is well-documented to increase the risk for PAH up to 300-fold, leading to HIV-Associated Pulmonary Arterial Hypertension (HA-PAH) in 1:200 HIV infected individuals. Previous research has shown that the viral protein Tat (trans-activator of transcription), is a major effector of oxidative stress in HIV patients. Two Tat isoforms are commonly detected during HIV infection, full-length Tat 101 and Tat 86 . Tat 101 is encoded by two exons, whereas Tat 86 is encoded by the first exon plus half of the second exon. It has been shown that deletion of the second exon has no substantial effect on HIV-1 LTR transactivation, and therefore the Tat 86 isoform has been sufficient for most HIV research to date. However little is known about the direct role of the second exon on subsequent oxidative stress and other cellular responses such as inflammation, proliferation or apoptosis. We measured nitrotyrosine content, carbonyl proteins, lipid peroxidation and total antioxidant capacity in Human Pulmonary Artery Endothelial cells (HPAEC) expressing either Tat 86 or Tat 101 to determine if both of the Tat isoforms induce oxidative stress in these pulmonary vascular cells that could contribute to HA-PAH.