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This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ohshima, S. Articles by Narula, J. PubMed Articles by Ohshima, S. Articles by Narula, J.

Molecular imaging of MMP expression in atherosclerosis in transgenic mouse models

¹ Division of Cardiology, University of California, Irvine School of Medicine, Irvine, California; ² Bristol-Myers Squibb Medical Imaging, North Billerica, Massachusetts; ³ Division of Cardiovascular Diseases, University of California, San Diego, La Jolla, California

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Objectives: Matrix Metalloproteinases (MMP) play an important role in atherosclerotic plaque instability by contributing to positive vascular remodeling and fibrous cap thinning and rupture.

Methods: Using a 99mTc-labeled broad spectrum MMP inhibitor (MPI) and micro-SPECT/micro CT, we evaluated the feasibility of noninvasive imaging of MMP activity in apolipoprotein E deficient (E0, n=14), low density lipoprotein receptor deficient (L0, n=14) mice and wild-type C57BL/6 mice (N=7). The mean age of the mice was 47 ± 3.3 weeks. Of these, 7 E0 and 7 L0 mice received a high cholesterol diet (HCD) for 6 months before imaging. After in vivo imaging, aortas were explanted, ex vivo images acquired and the percent injected dose per gram (%ID/g) MPI uptake determined, followed by histological and immunohistochemical characterization.

Results: MPI uptake was noninvasively visualized in atherosclerotic lesions by micro-SPECT imaging and confirmed by micro CT localization and aortic calcification. %ID/g MPI uptake in each part of aorta was highest in the HCD E0, followed by the HCD-L0, chow-fed E0 and L0. The control mice had minimal MPI uptake. A significant correlation was noted between MPI uptake and MMP-2 (r=.44, p=.10) and -9 (r=.65, p=.008) expression in atherosclerotic plaque.

Conclusions: This study demonstrates the feasibility of using radiolabeled MPI for noninvasive assessment of MMP activity in experimental atherosclerotic models and likelihood of eventual clinical identification of unstable plaques.

This Article Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ohshima, S. Articles by Narula, J. PubMed Articles by Ohshima, S. Articles by Narula, J.