Title:
Antiretroviral Drugs Efavirenz and Tenofovir and their Effects on Arterial Remodeling and Protease Activity

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Roberts, Ladeidra Monet
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Abstract
Highly antiretroviral therapies (HAART) have been implemented to slow the progression of the human immunodeficiency virus (HIV). Although these new advances in the medications for HIV-positive patients have contributed in longer life expectancy, comorbidities, such as cardiovascular disease, still cause higher number of deaths among HIV-positive patients than in the regular population. Because of the intrinsic inflammation caused by the HIV virus, atherogenesis is more likely to occur and is driven by infected macrophages. These macrophages are known to secrete cathepsins, but infection causes the macrophages not to perform their function properly as an immune agent. I hypothesize that antiretroviral drugs play an important role in arterial remodeling by affecting cells within the artery and causing an alteration of cathepsin activity, leading to an increased risk of atherosclerosis in HIV patients. To test this hypothesis, we incubated THP-1 monocytes with antiretroviral drugs efavirenz and tenofovir individually to observe any changes in cathepsin activity. These lysates were analyzed through multiplex cathepsin zymography and quantified through densitometry. We found that our hypothesis held true for efavirenz and tenofovir in THP-1 monocytes, which caused decreased cathepsin K activity compared to vehicle controls. Still, stimulation of peripheral blood mononuclear cells (PBMCs) with efavirenz and tenofovir caused differential effects. Together, our data suggest that the HAART interaction with monocytes that are physiologically relevant to our system possibly contributes to the advancement of atherogenesis in HIV+ patients.
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2014-04-01
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Undergraduate Thesis
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