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

• Type of Material: Article
• Authors: Laura Hansen, Emory University; Ivana Parker, Georgia Institute of Technology; Roy Sutliff, Emory University; Manu Omar Platt, Emory University; Rudolph L. Gleason, Jr., Georgia Institute of Technology
• Language: English
• Date: 2013-04-01
• Publisher: Springer (part of Springer Nature): Springer Open Choice Hybrid Journals
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Biomedical Engineering Society.
• Final Published Version (URL): http://dx.doi.org/10.1007/s10439-012-0702-5
• Title of Journal or Parent Work: Annals of Biomedical Engineering
• ISSN: 0090-6964
• Volume: 41
• Issue: 4
• Start Page: 682
• End Page: 693
• Grant/Funding Information: 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).
• Keywords: REVERSE-TRANSCRIPTASE INHIBITORS; Engineering; CORONARY-HEART-DISEASE; CAROTID-ARTERY; HIV; Vascular remodeling; Atherosclerosis; Science & Technology; INFECTED PATIENTS; RISK-FACTORS; ACTIVE ANTIRETROVIRAL THERAPY; REDUCES ATHEROSCLEROSIS; PROTEASE INHIBITORS; CATHEPSIN-K; Technology; MYOCARDIAL-INFARCTION; Engineering, Biomedical
• Research Categories: Engineering, Biomedical; Health Sciences, Medicine and Surgery

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.