Endothelial dysfunction, arterial stiffening, and intima-media thickening in large arteries from HIV-1 transgenic mice

Ann Biomed Eng. 2013 Apr;41(4):682-93. doi: 10.1007/s10439-012-0702-5. Epub 2012 Nov 22.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Atherosclerosis / etiology
  • Atherosclerosis / pathology
  • Atherosclerosis / physiopathology
  • Biomedical Engineering
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / pathology
  • Cardiovascular Diseases / physiopathology
  • Endothelium, Vascular / physiopathology
  • Endothelium, Vascular / virology
  • Genes, Viral
  • HIV Infections / complications
  • HIV-1 / genetics
  • HIV-1 / pathogenicity*
  • Human Immunodeficiency Virus Proteins / genetics
  • Human Immunodeficiency Virus Proteins / physiology*
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Tunica Intima / pathology
  • Tunica Intima / virology
  • Tunica Media / pathology
  • Tunica Media / virology
  • Vascular Stiffness / physiology


  • Human Immunodeficiency Virus Proteins