| First Author | Behm CZ | Year | 2008 |
| Journal | Circulation | Volume | 117 |
| Issue | 22 | Pages | 2902-11 |
| PubMed ID | 18506006 | Mgi Jnum | J:155083 |
| Mgi Id | MGI:4412236 | Doi | 10.1161/CIRCULATIONAHA.107.744037 |
| Citation | Behm CZ, et al. (2008) Molecular imaging of endothelial vascular cell adhesion molecule-1 expression and inflammatory cell recruitment during vasculogenesis and ischemia-mediated arteriogenesis. Circulation 117(22):2902-11 |
| abstractText | 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, 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. |
