J Korean Neurol Assoc.  2009 Feb;27(1):36-41.

Molecular Optical Imaging of Cathepsin-B Proteolytic Enzyme Activity to Reflect Atherosclerosis Pathophysiology and Anti-Atherosclerotic Therapeutic Effect

• Kim DE
• Kim JY
• Kim EJ
• Jeong SW

Abstract

BACKGROUND
Protease-sensing molecular optical imaging can potentially identify vulnerable atherosclerotic plaques before cerebral infarcts occur. However, several translational issues need to be resolved before implementing human trials and clinical applications of the technique. We investigated whether molecular optical imaging reflects (1) atherosclerosis pathophysiology and (2) the atherosclerosis-modulating effect of a Western diet or atorvastatin treatment in ApoE-knockout mice.
METHODS
We fed 21 8-week-old ApoE-knockout mice a normal chow diet (n=7), a Western diet (n=7), or a Western diet with atorvastatin (n=7) for 14 weeks. Blood was collected for measuring cholesterol levels at 24 hours after injecting the cathepsin-B (CatB) probe into the tail vein. Near-infrared fluorescence reflectance imaging of CatB activity was performed after excising the aorta.
RESULTS
CatB molecular optical imaging precisely reflected the pathophysiologic alteration of atherosclerosis. The CatB activity signal was significantly stronger in the Western diet group (49.3+/-26.0 [mean+/-SD], arbitrary units) than in the atorvastatin group (25.3+/-8.7) and the normal chow diet group (20.6+/-21.1). The effect of the statin on CatB activity was independent of cholesterol lowering.
CONCLUSIONS
CatB-sensing molecular optical imaging represents a valuable tool for evaluating atherosclerosis pathophysiology and for monitoring the effects of antiatherosclerotic therapeutic interventions.

Keyword

Molecular imaging; Atherosclerosis; Optical imaging; Cathepsin; Protease; Statin

MeSH Terms

Animals
Aorta
Atherosclerosis
Cathepsins
Cholesterol
Diet
Fluorescence
Heptanoic Acids
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Mice
Molecular Imaging
Optical Imaging
Plaque, Atherosclerotic
Pyrroles
Veins
Atorvastatin Calcium
Cathepsins
Cholesterol
Heptanoic Acids
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Pyrroles