Molecular Imaging of Interstitial Alterations in Remodeling Myocardium After Myocardial Infarction

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

卷:52

Article

van den Borne, Susanne W. M.²  Lovhaug, Dagfinn³  Frederik, Peter²  Arbo, Bente³  Rogstad, Astri³  Cuthbertson, Alan³  Chettibi, Salah³  Reutelingsperger, Chris²  Blankesteijn, W. Matthijs²  Smits, Jos F. M.²  Daemen, Mat J. A. P.²  Zannad, Faiez⁴  Pitt, Bertram⁵  Hofstra, Leonard²  Narula, Jagat¹ 

[1] Univ Calif Irvine, Div Cardiol, Sch Med, Orange, CA 92868 USA

[2] Maastricht Univ, Cardiovasc Res Inst Maastricht, Maastricht, Netherlands

[3] GE Healthcare AS, Oslo, Norway

[4] Univ Henri Poincare, Nancy, France

[5] Univ Michigan, Ann Arbor, MI 48109 USA

关键词: myofibroblasts;    integrins;    interstitial fibrosis;    radionuclide imaging;    heart failure;    coronary artery disease;   

DOI  :  10.1016/j.jacc.2008.07.067

来源: Elsevier

【 摘 要 】

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. (J Am Coll Cardiol 2008;52:2017-28) (C) 2008 by the American College of Cardiology Foundation

【 授权许可】

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