Molecular imaging of matrix metalloproteinase expression in atherosclerotic plaques of mice deficient in apolipoprotein e or low-density-lipoprotein receptor

Satoru Ohshima, Artiom Petrov, Shinichiro Fujimoto, Jun Zhou, Michael Azure, D. Scott Edwards, Toyoaki Murohara, Navneet Narula, Sotirios Tsimikas, Jagat Narula

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Matrix metalloproteinases (MMPs) are expressed in atherosclerotic plaques and play an important role in plaque instability. Methods: Using 99mTc-labeled broad-spectrum MMP inhibitor (MPI), we performed noninvasive imaging of MMP expression with micro-SPECT/micro-CT in mice deficient in apolipoprotein E (ApoE-/-, n = 14), mice deficient in low-density-lipoprotein receptor (LDLR-/-, n = 14), and C57/BL6 mice as controls (n = 7). Seven ApoE-/- and 7 LDLR-/- received a high-cholesterol diet. After in vivo imaging, aortas were explanted, ex vivo images acquired, and the percent injected dose of MPI per gram (%ID/g) determined, followed by histologic characterization of atherosclerotic lesions. Results: MPI uptake was noninvasively visualized in atherosclerotic lesions by micro-SPECT, with confirmation by micro-CT of anatomic location and aortic calcification. %ID/g in each part of the aorta was highest in ApoE-/- that were fed a high-cholesterol diet, followed by LDLR-/- that were fed a high-cholesterol diet, ApoE-/- that were fed normal chow, and LDLR-/- that were fed normal chow. The control mice had minimal MPI uptake. A significant correlation was noted between %ID/gand %area positive for macrophages (r = 0.81, P = 0.009), MMP-2 (r = 0.65, P = 0.013), and MMP-9 (r = 0.62, P = 0.008). Conclusion: This study demonstrates the usefulness of molecular imaging for noninvasive assessment of the extent of MMP expression in various transgenic mouse models of atherosclerosis receiving a normal or hyperlipidemic diet. It is conceivable that such a strategy may be translationally developed for identification of unstable atherosclerotic plaques. COPYRIGHT

Original languageEnglish
Pages (from-to)612-617
Number of pages6
JournalJournal of Nuclear Medicine
Volume50
Issue number4
DOIs
StatePublished - 1 Apr 2009
Externally publishedYes

Keywords

  • Apolipoprotein e-deficient mice
  • Atherosclerosis
  • Low-density-lipoprotein receptor-deficient mice
  • Plaque rupture
  • Radionuclide imaging

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