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Arterioscler Thromb Vasc Biol. 2012 Nov;32(11):2616-24. doi: 10.1161/ATVBAHA.112.251983. Epub 2012 Sep 20.

Inflammation modulates murine venous thrombosis resolution in vivo: assessment by multimodal fluorescence molecular imaging.

Author information

1
Harvard Medical School, Massachusetts General Hospital, Cardiovascular Research Center, 185 Cambridge St, Suite 3206, Boston, MA 02114, USA.

Abstract

OBJECTIVE:

Assessment of thrombus inflammation in vivo could provide new insights into deep vein thrombosis (DVT) resolution. Here, we develop and evaluate 2 integrated fluorescence molecular-structural imaging strategies to quantify DVT-related inflammation and architecture and to assess the effect of thrombus inflammation on subsequent DVT resolution in vivo.

METHODS AND RESULTS:

Murine DVT were created with topical 5% FeCl(3) application to thigh or jugular veins (n=35). On day 3, mice received macrophage and matrix metalloproteinase activity fluorescence imaging agents. On day 4, integrated assessment of DVT inflammation and architecture was performed using confocal fluorescence intravital microscopy. Day 4 analyses showed robust relationships among in vivo thrombus macrophages, matrix metalloproteinase activity, and fluorescein isothiocyanate-dextran deposition (r>0.70; P<0.01). In a serial 2-time point study, mice with DVT underwent intravital microscopy at day 4 and day 6. Analyses revealed that the intensity of thrombus inflammation at day 4 predicted the magnitude of DVT resolution at day 6 (P<0.05). In a second approach, noninvasive fluorescence molecular tomography-computed tomography was used and detected macrophages within jugular DVT (P<0.05 versus sham controls).

CONCLUSIONS:

Integrated fluorescence molecular-structural imaging demonstrates that the DVT-induced inflammatory response can be readily assessed in vivo and can inform the magnitude of thrombus resolution.

PMID:
22995524
PMCID:
PMC3516622
DOI:
10.1161/ATVBAHA.112.251983
[Indexed for MEDLINE]
Free PMC Article

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