Molecular imaging of endothelial vascular cell adhesion molecule-1 expression and inflammatory cell recruitment during vasculogenesis and ischemia-mediated arteriogenesis

Carolyn Z. Behm, Beat A. Kaufmann, Chad Carr, Miles Lankford, John M. Sanders, C. Edward Rose, Sanjiv Kaul, Jonathan R. Lindner

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    103 Scopus citations

    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. METHODS AND RESULTS - Contrast ultrasound perfusion imaging and molecular imaging with microbubbles targeted to activated neutrophils, α5-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 α5-integrins and VCAM-1 coincided with the earliest appearance of regional blood flow. Targeted imaging correlated temporally with histological evidence of channel formation by α5-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 α5-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.

    Original languageEnglish (US)
    Pages (from-to)2902-2911
    Number of pages10
    JournalCirculation
    Volume117
    Issue number22
    DOIs
    StatePublished - Jun 1 2008

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    Keywords

    • Angiogenesis
    • Echocardiography
    • Imaging
    • Inflammation

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine
    • Physiology (medical)

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