title: Analysis of in situ and ex vivo αVβ3 integrin expression during experimental carotid atherogenesis.
abstract: OBJECTIVE
  Mural inflammation has been shown to contribute to the development of plaque, with the α(V)β(3) integrin highly expressed in atherosclerotic plaques. We herein examined α(V)β(3) integrin expression as a function of carotid atherosclerosis formation in the apolipoprotein E-deficient (apoE(-/-)) mouse.
  
  
  RESULTS
  Constrictive collars were placed around the left common carotid arteries of apo E(-/-) mice maintained on a high-fat diet (n = 14). Before and 21 days following collar placement, in vivo serial magnetic resonance imaging (MRI) measurements of the carotid aortic diameter were performed using a 7T magnetic resonance (MR) scanner. Near- infrared fluorescence (NIRF) imaging was performed (n = 6) using an in vivo imaging system 0-24 hours following administration of 1.0 nmol c(RGDyK)-Cy5.5 via the tail vein. A competition experiment was performed by the co-injection of a saturating dose of bicyclic RGD peptide H-Glu[cyclo(Arg-Gly-Asp-D-Tyr-Lys)]2 (n = 3). Following image acquisition and sacrifice at 24 hours after injection, carotid arteries were harvested for histological analyses. Neointima formation and arterial remodeling in the carotid arteries of apoE(-/-) mice were induced by the placement of a constrictive collar. Significantly greater fluorescent signals were obtained from constrictive collar left common carotid arteries as compared to uninvolved aortic segments in constrictive collar mice. Binding to stenotic lesions was efficiently blocked in competition experiments. Immunostaining confirmed the presence of mural α(V)β(3) integrin expression in macrophages in the neointima. Signal intensity increased in a macrophage density-dependent fashion in the stenotic segments.
  
  
  CONCLUSIONS
  Mural α(V)β(3) integrin expression, as determined using RGD-Cy5.5 near-infrared optical imaging, was increased in carotid arteries with constrictive collars in experimental mice. This expression can estimate the macrophage-bound inflammatory activity of atherosclerotic lesions.
authors.affiliation: Department of Cardiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu, People's Republic of China.
authors.forename: Yuyu
authors.initials: Y
authors.lastname: Yao
authors.forename: Yibo
authors.initials: Y
authors.lastname: Jiang
authors.forename: Zulong
authors.initials: Z
authors.lastname: Sheng
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yanli
authors.initials: Y
authors.lastname: An
authors.forename: Fengdi
authors.initials: F
authors.lastname: Yan
authors.forename: Genshan
authors.initials: G
authors.lastname: Ma
authors.forename: Naifeng
authors.initials: N
authors.lastname: Liu
authors.forename: Gaojun
authors.initials: G
authors.lastname: Teng
authors.forename: Zhen
authors.initials: Z
authors.lastname: Cheng
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001024:Aortic Valve Stenosis / Q000378:metabolism; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000473:pathology; D016893:Carotid Stenosis / Q000378:metabolism / Q000473:pathology; D059305:Diet, High-Fat; D006651:Histocytochemistry; D039302:Integrin alphaVbeta3 / Q000096:biosynthesis*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D058426:Neointima / Q000378:metabolism; D019265:Spectroscopy, Near-Infrared
chemical_list: D039302:Integrin alphaVbeta3