Dual molecular imaging for targeting metalloproteinase activity and apoptosis in atherosclerosis: Molecular imaging facilitates understanding of pathogenesis

Nezam Haider, Dagmar Hartung, Shinichiro Fujimoto, Artiom Petrov, Frank D. Kolodgie, Renu Virmani, Satoru Ohshima, Han Liu, Jun Zhou, Ai Fujimoto, Atsuko Tahara, Leo Hofstra, Navneet Narula, Chris Reutelingsperger, Jagat Narula

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Background: Macrophage apoptosis and MMP activity contribute to vulnerability of atherosclerotic plaques to rupture. By employing molecular imaging techniques, we investigated if apoptosis and MMP release are interlinked. Methods: Atherosclerosis was produced in rabbits receiving high-cholesterol diet (HC), who underwent dual radionuclide imaging with 99mTc-labeled matrix metalloproteinase inhibitor (MPI) and 111In-labeled annexin A5 (AA5) using micro-SPECT/CT. %ID/g MPI and AA5 uptake was measured, followed by histological characterization. Unmanipulated animals were used as disease controls. Correlation between MPI and AA5 uptake was undertaken and relationship confirmed in culture study of activated THP-1 monocytes. Results: MPI and AA5 uptake was best visualized in HC diet animals (n = 6) and reduced significantly after fluvastatin treatment (n = 4) or diet withdrawal (n = 3). %ID/g MPI (.087 ± .018%) and AA5 (.03 ± .01%) uptake was higher in HC than control (n = 6) animals (.014 ± .004%, P < .0001; .0007 ± .0002%, P < .0001), and reduced substantially after diet or statin intervention. There was a significant correlation between MPI and AA5 uptake (r = .62, P < .0001), both correlated with pathologically verified MMP-9 activity, macrophage content, and TUNEL staining. In vitro studies demonstrated MMP-9 release in culture medium from apoptotic THP-1 monocytes. Conclusions: The present study suggests that apoptosis and MMP are interrelated in atherosclerotic lesions and the targeting of more than one molecular candidate is feasible by molecular imaging.

Original languageEnglish
Pages (from-to)753-762
Number of pages10
JournalJournal of Nuclear Cardiology
Volume16
Issue number5
DOIs
StatePublished - 2009
Externally publishedYes

Keywords

  • Radionuclides
  • SPECT
  • Vulnerable atherosclerotic plaque

Fingerprint

Dive into the research topics of 'Dual molecular imaging for targeting metalloproteinase activity and apoptosis in atherosclerosis: Molecular imaging facilitates understanding of pathogenesis'. Together they form a unique fingerprint.

Cite this