Annals of Biomedical Engineering

, Volume 41, Issue 4, pp 682–693 | Cite as

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

  • Laura Hansen
  • Ivana Parker
  • Roy L. Sutliff
  • Manu O. Platt
  • Rudolph L. GleasonJr.
Article

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.

Keywords

HIV Atherosclerosis Vascular remodeling 

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Copyright information

© Biomedical Engineering Society 2012

Authors and Affiliations

  • Laura Hansen
    • 1
  • Ivana Parker
    • 2
  • Roy L. Sutliff
    • 3
  • Manu O. Platt
    • 1
    • 4
  • Rudolph L. GleasonJr.
    • 1
    • 2
    • 4
  1. 1.The Wallace H. Coulter Department of Biomedical EngineeringGeorgia Institute of TechnologyAtlantaUSA
  2. 2.The George W. Woodruff School of Mechanical EngineeringGeorgia Institute of TechnologyAtlantaUSA
  3. 3.Department MedicineEmory University/Atlanta VAMCAtlantaUSA
  4. 4.The Petit Institute for Bioengineering and BiosciencesGeorgia Institute of TechnologyAtlantaUSA

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