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J Nucl Cardiol. 2014 Apr;21(2):319-328. doi: 10.1007/s12350-013-9843-7. Epub 2013 Dec 25.

Lipid lowering and imaging protease activation in atherosclerosis.

Author information

1
Cardiovascular Molecular Imaging Laboratory, Section of Cardiovascular Medicine and Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT.
2
VA Connecticut Healthcare System, West Haven, CT.
3
Lantheus Medical Imaging, North Billerica, MA.
#
Contributed equally

Abstract

BACKGROUND:

Lipid lowering is a mainstay of modern therapeutic approach to atherosclerosis. We sought to evaluate matrix metalloproteinase (MMP)-targeted microSPECT imaging for tracking of the effect of lipid-lowering interventions on plaque biology in atherosclerotic mice in vivo.

METHODS AND RESULTS:

ApoE(-/-) mice fed on a high fat diet (HFD) for 2 months were randomly assigned to continuation of HFD, HFD plus simvastatin, HFD plus fenofibrate and high fat withdrawal (HFW). The animals underwent serial microSPECT/CT imaging using RP805, a (99m)Tc-labeled MMP-targeted tracer at 1 and 4 weeks after randomization. All three interventions reduced total blood cholesterol by 4 weeks. In animals on HFD, aortic arch RP805 uptake significantly increased from 1 week to 4 weeks. Tracer uptake in fenofibrate and HFW groups was significantly lower than uptake in the HFD group at 4 weeks. Similarly, CD 68 gene expression, reflecting plaque inflammation, was significantly lower in fenofibrate and HFW groups compared to HFD group. MMP tracer uptake significantly correlated with aortic CD68, but not VE-cadherin or smooth muscle α-actin expression.

CONCLUSIONS:

MMP tracer uptake paralleled the effect of lipid-lowering interventions on plaque inflammation in atherosclerotic mice. MMP-targeted imaging may be used to track the effect of therapeutic interventions in atherosclerosis.

PMID:
24368425
PMCID:
PMC3991560
DOI:
10.1007/s12350-013-9843-7
[Indexed for MEDLINE]
Free PMC Article

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