title: Plaque-associated vasa vasorum in aged apolipoprotein E-deficient mice exhibit proatherogenic functional features in vivo.
abstract: OBJECTIVE
  Neovascularization of human atherosclerotic plaques is implicated in plaque progression and destabilization, although its functional implications are yet unresolved. Here, we aimed to elucidate functional and morphological properties of plaque microvessels in mice in vivo.
  
  
  RESULTS
  Atherosclerotic carotid arteries from aged (>40 weeks) apolipoprotein E-deficient mice were imaged in vivo using multiphoton laser scanning microscopy. Two distinct groups of vasa vasorum microvessels were observed at sites of atherosclerosis development (median diameters of 18.5 and 5.9 μm, respectively), whereas microvessels within the plaque could only rarely be found. In vivo imaging showed ongoing angiogenic activity and injection of fluorescein isothiocyanate-dextran confirmed active perfusion. Plaque vasa vasorum showed increased microvascular leakage, combined with a loss of endothelial glycocalyx. Mean blood flow velocity in plaque-associated vasa vasorum was reduced by ±50% compared with diameter-matched control capillaries, whereas mean blood flow was reduced 8-fold. Leukocyte adhesion and extravasation were increased 6-fold in vasa vasorum versus control capillaries.
  
  
  CONCLUSIONS
  Using a novel in vivo functional imaging strategy, we showed that plaque-associated vasa vasorum were angiogenically active and, albeit poorly, perfused. Moreover, plaque-associated vasa vasorum showed increased permeability, reduced blood flow, and increased leukocyte adhesion and extravasation (ie, characteristics that could contribute to plaque progression and destabilization).
authors.affiliation: Maastricht University, P. Debyelaan 25, Maastricht, 6229HX, the Netherlands. t.rademakers@maastrichtuniversity.nl
authors.forename: Timo
authors.initials: T
authors.lastname: Rademakers
authors.forename: Kim
authors.initials: K
authors.lastname: Douma
authors.forename: Tilman M
authors.initials: TM
authors.lastname: Hackeng
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Post
authors.forename: Judith C
authors.initials: JC
authors.lastname: Sluimer
authors.forename: Mat J A P
authors.initials: MJ
authors.lastname: Daemen
authors.forename: Erik A L
authors.initials: EA
authors.lastname: Biessen
authors.forename: Sylvia
authors.initials: S
authors.lastname: Heeneman
authors.forename: Marc A M J
authors.initials: MA
authors.lastname: van Zandvoort
mesh_terms: D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001783:Blood Flow Velocity; D002199:Capillary Permeability; D002339:Carotid Arteries / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion; D004195:Disease Models, Animal; D018450:Disease Progression; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008833:Microcirculation; D018613:Microscopy, Confocal; D036641:Microscopy, Fluorescence, Multiphoton; D055806:Microvessels / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009389:Neovascularization, Pathologic; D058226:Plaque, Atherosclerotic; D012039:Regional Blood Flow; D013997:Time Factors; D014651:Vasa Vasorum / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: D001057:Apolipoproteins E