Lipid lowering and imaging protease activation in atherosclerosis

• Published in: Journal of nuclear cardiology 2014-04, Vol.21 (2), p.319-328
• Main Authors: Razavian, Mahmoud, Nie, Lei, Challa, Azariyas, Zhang, Jiasheng, Golestani, Reza, Jung, Jae-Joon, Robinson, Simon, Sadeghi, Mehran M.
• Format: Article
• Language: English
• Subjects: Animals; Atherosclerosis; Atherosclerosis - diet therapy; Atherosclerosis - metabolism; Cardiology; Combined Modality Therapy; Dietary Fats - metabolism; Enzyme Activation; Female; Hypolipidemic Agents - therapeutic use; Imaging; inflammation; Lipid Metabolism; lipids; matrix metalloproteinases; Matrix Metalloproteinases - metabolism; Medicine; Medicine & Public Health; Mice; Mice, Knockout; molecular imaging; Molecular Imaging - methods; Nuclear Medicine; Original Article; Radiology; Reproducibility of Results; Sensitivity and Specificity; Treatment Outcome
• ISSN: 1071-3581; 1532-6551
• DOI: 10.1007/s12350-013-9843-7

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. 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 99mTc-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. 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.