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Arterioscler Thromb Vasc Biol. 2011 Jan;31(1):102-9. doi: 10.1161/ATVBAHA.110.216036. Epub 2010 Oct 14.

Matrix metalloproteinase activation predicts amelioration of remodeling after dietary modification in injured arteries.

Author information

1
Veterans Affairs, Connecticut Healthcare System, West Haven, CT 06516, USA.

Abstract

OBJECTIVE:

To establish and validate early noninvasive imaging of matrix metalloproteinase (MMP) activation for monitoring the progression of vascular remodeling and response to dietary modification.

METHODS AND RESULTS:

Apolipoprotein E(-/-) mice that were fed a high-fat diet underwent left common carotid artery wire injury. One week after surgery, a group of animals were withdrawn from the high-fat diet. The other group of animals continued that diet throughout the study. Micro single-photon emission computed tomographic (microSPECT)/CT imaging with RP805 (a (99m)Tc-labeled tracer targeting activated MMPs) was repeatedly performed at 2 and 4 weeks after surgery. Histological analysis at 4 weeks showed significant left carotid neointima formation, monocyte/macrophage infiltration, and upregulation of several MMPs, which were ameliorated by withdrawal from the high-fat diet. In vivo microSPECT/CT images visualized significant RP805 uptake, reflecting MMP activation, in the injured carotid arteries. MMP activation was reduced as early as 1 week after withdrawal from the high-fat diet and significantly correlated with neointimal area at 4 weeks after surgery.

CONCLUSIONS:

MMP activation predicts the progression of vascular remodeling and can track the effect of dietary modification after vascular injury.

PMID:
20947820
PMCID:
PMC3005135
DOI:
10.1161/ATVBAHA.110.216036
[Indexed for MEDLINE]
Free PMC Article

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