Molecular Imaging of Interstitial Alterations in Remodeling Myocardium After Myocardial Infarction

Susanne W.M. van den Borne, Satoshi Isobe, Johan W. Verjans, Artiom Petrov, Dagfinn Lovhaug, Peng Li, H. Reinier Zandbergen, Youping Ni, Peter Frederik, Jun Zhou, Bente Arbo, Astri Rogstad, Alan Cuthbertson, Salah Chettibi, Chris Reutelingsperger, W. Matthijs Blankesteijn, Jos F.M. Smits, Mat J.A.P. Daemen, Faiez Zannad, Mani A. VannanNavneet Narula, Bertram Pitt, Leonard Hofstra, Jagat Narula

Research output: Contribution to journalArticlepeer-review

135 Scopus citations

Abstract

Objectives: The purpose of this study was to evaluate interstitial alterations in myocardial remodeling using a radiolabeled Cy5.5-RGD imaging peptide (CRIP) that targets myofibroblasts. Background: Collagen deposition and interstitial fibrosis contribute to cardiac remodeling and heart failure after myocardial infarction (MI). Evaluation of myofibroblastic proliferation should provide indirect evidence of the extent of fibrosis. Methods: Of 46 Swiss-Webster mice, MI was induced in 41 by coronary artery occlusion, and 5 were unmanipulated. Of the 41 mice, 6, 6, and 5 received intravenous technitium-99m labeled CRIP for micro-single-photon emission computed tomography imaging 2, 4, and 12 weeks after MI, respectively; 8 received captopril or captopril with losartan up to 4 weeks after MI. Scrambled CRIP was used 4 weeks after MI in 6 mice; the remaining 10 of 46 mice received unradiolabeled CRIP for histologic characterization. Results: Maximum CRIP uptake was observed in the infarct area; quantitative uptake (percent injected dose/g) was highest at 2 weeks (2.75 ± 0.46%), followed by 4 (2.26 ± 0.09%) and 12 (1.74 ± 0.24%) weeks compared with that in unmanipulated mice (0.59 ± 0.19%). Uptake was higher at 12 weeks in the remote areas. CRIP uptake was histologically traced to myofibroblasts. Captopril alone (1.78 ± 0.31%) and with losartan (1.13 ± 0.28%) significantly reduced tracer uptake; scrambled CRIP uptake in infarct area (0.74 ± 0.17%) was similar to CRIP uptake in normal myocardium. Conclusions: Radiolabeled CRIP allows for noninvasive visualization of interstitial alterations during cardiac remodeling, and is responsive to antiangiotensin treatment. If proven clinically feasible, such a strategy would help identify post-MI patients likely to develop heart failure.

Original languageEnglish
Pages (from-to)2017-2028
Number of pages12
JournalJournal of the American College of Cardiology
Volume52
Issue number24
DOIs
StatePublished - 9 Dec 2008
Externally publishedYes

Keywords

  • coronary artery disease
  • heart failure
  • integrins
  • interstitial fibrosis
  • myofibroblasts
  • radionuclide imaging

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