title: Molecular imaging of endothelial vascular cell adhesion molecule-1 expression and inflammatory cell recruitment during vasculogenesis and ischemia-mediated arteriogenesis.
abstract: BACKGROUND
  Inflammatory responses contribute to vascular remodeling during tissue repair or ischemia. We hypothesized that inflammatory cell recruitment and endothelial cell activation during vasculogenesis and ischemia-mediated arteriogenesis could be temporally assessed by noninvasive molecular imaging.
  
  
  RESULTS
  Contrast ultrasound perfusion imaging and molecular imaging with microbubbles targeted to activated neutrophils, alpha(5)-integrins, or vascular cell adhesion molecule (VCAM-1) were performed in murine models of vasculogenesis (subcutaneous matrigel) or hind-limb ischemia produced by arterial occlusion in wild-type or monocyte chemotactic protein-1-deficient mice. In subcutaneous matrigel plugs, perfusion advanced centripetally between days 3 and 10. On targeted imaging, signal enhancement from alpha(5)-integrins and VCAM-1 coincided with the earliest appearance of regional blood flow. Targeted imaging correlated temporally with histological evidence of channel formation by alpha(5)-integrin-positive monocytes, followed by the appearance of spindle-shaped cells lining the channels that expressed VCAM-1. In ischemic hind-limb tissue, skeletal muscle blood flow and arteriolar density increased progressively between days 2 and 21 after arterial ligation. Targeted imaging demonstrated early signal enhancement for neutrophils, monocyte alpha(5)-integrin, and VCAM-1 at day 2 when blood flow was very low (<20% control). The neutrophil signal declined precipitously between days 2 and 4, whereas VCAM-1 and monocyte signal persisted to day 7. In mice deficient for monocyte chemotactic protein-1, monocyte-targeted signal was severely reduced compared with wild-type mice (1.2+/-0.6 versus 10.5+/-8.8 video intensity units on day 4; P<0.05), although flow responses were only mildly impaired.
  
  
  CONCLUSIONS
  Different components of the inflammatory response that participate in vascular development and remodeling can be assessed separately with targeted molecular imaging.
authors.affiliation: Division of Cardiovascular Medicine, Oregon Health and Science University, 3181 SW Sam Jackson Park Rd, Portland, OR 97239, USA.
authors.forename: Carolyn Z
authors.initials: CZ
authors.lastname: Behm
authors.forename: Beat A
authors.initials: BA
authors.lastname: Kaufmann
authors.forename: Chad
authors.initials: C
authors.lastname: Carr
authors.forename: Miles
authors.initials: M
authors.lastname: Lankford
authors.forename: John M
authors.initials: JM
authors.lastname: Sanders
authors.forename: C Edward
authors.initials: CE
authors.lastname: Rose
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Kaul
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Lindner
mesh_terms: D000818:Animals; D002633:Chemotaxis; D003952:Diagnostic Imaging / Q000379:methods*; D004730:Endothelium, Vascular / Q000737:chemistry / Q000502:physiology; D007249:Inflammation / Q000473:pathology*; D039482:Integrin alpha5 / Q000032:analysis; D007511:Ischemia; D051379:Mice; D045423:Microbubbles; D009000:Monocytes / Q000737:chemistry / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply; D018919:Neovascularization, Physiologic; D018375:Neutrophil Activation; D012039:Regional Blood Flow; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis*
chemical_list: D039482:Integrin alpha5; D019010:Vascular Cell Adhesion Molecule-1