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

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Abstract

HIV patients on highly active antiretroviral therapy (HAART) exhibit elevated incidence of cardiovascular disease (CVD), 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 (c-IMT), 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 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 CVD.

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Acknowledgments

We gratefully acknowledge the support from the National Institutes of Health and the International AIDS Society through the Creative and Novel Ideas in HIV Research (CNIHR) Program, the American Heart Association (11GRNT7990055), and the National Science Foundation Graduate Research Fellowship Program (LH).

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Authors and Affiliations

  1. The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA

    Laura Hansen, Manu O. Platt & Rudolph L. Gleason Jr.

  2. The George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA

    Ivana Parker & Rudolph L. Gleason Jr.

  3. Department Medicine, Emory University/Atlanta VAMC, Atlanta, GA, USA

    Roy L. Sutliff

  4. The Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA

    Manu O. Platt & Rudolph L. Gleason Jr.

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  1. Laura Hansen
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Hansen, L., Parker, I., Sutliff, R.L. et al. Endothelial Dysfunction, Arterial Stiffening, and Intima-Media Thickening in Large Arteries from HIV-1 Transgenic Mice. Ann Biomed Eng 41, 682–693 (2013). https://doi.org/10.1007/s10439-012-0702-5

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