title: Efavirenz treatment causes arterial stiffening in apolipoprotein E-null mice.
abstract: The development of highly active antiretroviral therapy (HAART) has transformed HIV-1 infection from a terminal diagnosis to a chronic, yet manageable disease. However, people living with HIV-1 exhibit a host of non-AIDS-related co-morbidities including cardiovascular disease (CVD). Several HAART drugs have been implicated in the development of CVD; however, the role of efavirenz (EFV), a highly prescribed HAART drug, in early-onset CVD is poorly understood. We treated apolipoprotein E-null (ApoE(-/-)) mice with EFV (75 mg/kg/day) or vehicle, via oral gavage, for 35 days and quantified commonly measured preclinical markers of CVD (intima-media thickening, arterial stiffening) and plaque area. Suprarenal abdominal aortas were subjected to cylindrical biaxial biomechanical testing and standard histology. Aortas from EFV-treated mice demonstrated decreased compliance (i.e., increased arterial stiffness) and decreased axial force and a trend toward decreased in vivo axial stretch, but EFV treatment had no effect on intima-media thickness of the aortic wall or plaque coverage in thoracic aortas and aortic arches. Taken together, these data suggest that EFV leads to arterial stiffening but, for the dose and duration tested, did not lead to elevated plaque progression in ApoE(-/-) mice.
authors.affiliation: The George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 315 Ferst Drive, IBB 2305, Atlanta, GA 30332, USA.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Caulk
authors.affiliation: The George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 315 Ferst Drive, IBB 2305, Atlanta, GA 30332, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Soler
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 315 Ferst Drive, IBB 2305, Atlanta, GA 30332, USA; The Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Drive, IBB 2305, Atlanta, GA 30332, USA.
authors.forename: Manu O
authors.initials: MO
authors.lastname: Platt
authors.affiliation: The George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 315 Ferst Drive, IBB 2305, Atlanta, GA 30332, USA; The Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, 315 Ferst Drive, IBB 2305, Atlanta, GA 30332, USA; The Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Drive, IBB 2305, Atlanta, GA 30332, USA. Electronic address: rudy.gleason@me.gatech.edu.
authors.forename: Rudolph L
authors.initials: RL
authors.lastname: Gleason
mesh_terms: D000480:Alkynes; D000818:Animals; D019380:Anti-HIV Agents / Q000009:adverse effects*; D001012:Aorta, Abdominal / Q000187:drug effects / Q000473:pathology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism; D048588:Benzoxazines / Q000009:adverse effects*; D059168:Carotid Intima-Media Thickness; D003521:Cyclopropanes; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000473:pathology; D066253:Vascular Remodeling; D059289:Vascular Stiffness / Q000187:drug effects*
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D001057:Apolipoproteins E; D048588:Benzoxazines; D003521:Cyclopropanes; C098320:efavirenz
keywords: Arterial stiffening; Atherosclerosis; Efavirenz; HAART; Vascular remodeling