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

J Korean Neurol Assoc > Volume 27(1); 2009 > Article

Journal of the Korean Neurological Association 2009;27(1): 36-41.

동맥경화 병태생리 및 치료 효과를 탐지하는 Cathepsin-B 단백분해효소 활성도 광학 분자영상

김동억, 김정연 김어진a 정상욱

동국대학교 의과대학 일산병원 신경과, 병리과a

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

Dong-Eog Kim

Molecular Imaging and Neurovascular Research (MINER) Laboratory, Departments of Neurology and Pathologya, Dongguk University International Hospital, Goyang, Korea

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. Key Words: Molecular imaging, Atherosclerosis, Optical imaging, Cathepsin, Protease, Statin