Abstract 16469: Human Immunodeficiency Virus (HIV)-Transgenic Rats Display Induced Expression of Vascular Factors Associated With Atherosclerosis
Multiple epidemiological studies have reported that HIV-infected individuals have a significantly increased risk of cardiovascular disease and clinical events. Study findings report cardiovascular effects of both the HIV virus itself, and also the antiretroviral therapies taken by HIV-patients; however, numerous studies shown that HIV is an independent risk factor for premature atherosclerosis. Several conditions including inflammation, metabolic syndrome, endothelial dysfunction, and altered lipid profiles are associated with HIV infection, each (or all) of which may contribute to accelerated atherosclerosis in these patients. There are limited suitable in vivo models available to study the effects of HIV on the vasculature without confounding factors such as antiretroviral therapies. We tested the hypothesis that the HIV transgenic (Tg) rat, which have seven of the nine HIV viral proteins (there is a functional deletion of Gag and Pol within the HIV-1 provirus to render the animals noninfectious) show altered oxidized lipid levels, as well as an increase in expression of monocyte/macrophage adhesion and infiltration in their vasculature. To test this hypothesis, we analyzed the vasculature of 3 mo old male HIV Tg rats (n=9) and compared findings to age matched F344 (genetic background for HIV Tg rats) male rats (n=9). Our findings show that plasma oxLDL and its endothelial cell receptor, the lectin like oxLDL (LOX)-1 receptor are both significantly upregulated in aortas of HIV Tg rats, compared to F344 rats. Furthermore, we measured an increase in monocyte chemoattractant protein (MCP)-1 mRNA and monocyte/macrophage (MOMA)-2 staining in the vasculature of these animals, associated with macrophage infiltration. Vascular endothelin (ET)-1 levels are also elevated in the HIV Tg rats, compared to F344 rats, suggesting the presence of endothelial dysfunction in these rats as well. These preliminary findings suggest that the HIV Tg rat may serve as a novel model for investigation of mechanisms of HIV-associated atherosclerosis, as they display altered oxLDL, increased monocyte signaling and vascular macrophage infiltration, and elevated ET-1, which represent multiple known pathways of atherogenesis and progression of vascular disease.
- © 2011 by American Heart Association, Inc.