title: Endothelial dysfunction, arterial stiffening, and intima-media thickening in large arteries from HIV-1 transgenic mice.
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.
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Hansen
authors.forename: Ivana
authors.initials: I
authors.lastname: Parker
authors.forename: Roy L
authors.initials: RL
authors.lastname: Sutliff
authors.forename: Manu O
authors.initials: MO
authors.lastname: Platt
authors.forename: Rudolph L
authors.initials: RL
authors.lastname: Gleason
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D001698:Biomedical Engineering; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology / Q000821:virology; D005814:Genes, Viral; D015658:HIV Infections / Q000150:complications; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity*; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017539:Tunica Intima / Q000473:pathology / Q000821:virology; D017540:Tunica Media / Q000473:pathology / Q000821:virology; D059289:Vascular Stiffness / Q000502:physiology
chemical_list: D054298:Human Immunodeficiency Virus Proteins