Endothelial Dysfunction, Arterial Stiffening, and Intima-Media Thickening in Large Arteries from HIV-1 Transgenic Mice

Autor: Laura Hansen, Rudolph L. Gleason, Manu O. Platt, Roy L. Sutliff, Ivana Parker
Rok vydání: 2012
Předmět:
Zdroj: Annals of Biomedical Engineering. 41:682-693
ISSN: 1573-9686
0090-6964
DOI: 10.1007/s10439-012-0702-5
Popis: HIV patients on highly active antiretroviral therapy (HAART) exhibit elevated incidence of cardiovascular disease, including a higher risk of myocardial infarction and prevalence of atherosclerotic lesions, as well as increases in markers of subclinical atherosclerosis including increased carotid artery intima-media thickness, increased arterial stiffness, and impaired flow-mediated dilation. Both HAART and HIV-infection are independent risk factors for atherosclerosis and myocardial infarction. Studies implicate the HIV proteins tat, gp120, vpu, and nef in early on-set atherosclerosis. The objective of this study was to quantify the role of expression of HIV-1 proteins on the vascular function, biomechanics, and geometry of common carotid arteries and aortas. This study employed NL4-3Δ gag/pol transgenic mice (HIV-Tg), which contain the genetic sequence for the HIV-1 proteins env, tat, nef, rev, vif, vpr, and vpu but lacks the gag and pol genes and reports that HIV-Tg mice have impaired aortic endothelial function, increased carotid intima-media thickness (c-IMT), and increased arterial stiffness. Further, HIV-Tg arteries show decreased elastin content, increased cathepsin K and cathepsin S activity, and increased mechanical residual stress. Thus, mice that express HIV proteins exhibit pre-clinical markers of atherosclerosis and these markers correlate with changes in markers of vascular remodeling. These findings are consistent with the hypothesis that HIV-proteins, independent of HAART treatment or HIV infection, could play a role in of the development of cardiovascular disease.
Databáze: OpenAIRE
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