Noninvasive Molecular Imaging of Cell Death in Myocardial Infarction using In-111-GSAO

Autor: Jagat Narula, Jun Zhou, Navneet Narula, Tsutomu Imaizumi, Riemer H. J. A. Slart, Raghu Pandurangi, Nobuhiro Tahara, Chris P. M. Reutelingsperger, Tiziano M. Scarabelli, Hans J. de Haas, Annapoorna Kini, Mary Dyszlewski, Takayoshi Yamaki, H. Reinier Zandbergen, Valentin Fuster, Artiom Petrov
Přispěvatelé: Banyu Life Science Foundation International, Dutch Heart Association, National Institutes of Health (Estados Unidos), Vascular Ageing Programme (VAP), Cardiovascular Centre (CVC), Translational Immunology Groningen (TRIGR), Carim, RS: CARIM - R1 - Thrombosis and haemostasis, RS: CARIM - R2 - Cardiac function and failure, CTC, Biochemie, Cardiologie
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: Scientific Reports
Scientific Reports, 4:6826. Nature Publishing Group
Repisalud
Instituto de Salud Carlos III (ISCIII)
ISSN: 2045-2322
Popis: Acute insult to the myocardium is associated with substantial loss of cardiomyocytes during the process of myocardial infarction. In this setting, apoptosis (programmed cell death) and necrosis may operate on a continuum. Because the latter is characterized by the loss of sarcolemmal integrity, we propose that an appropriately labeled tracer directed at a ubiquitously present intracellular moiety would allow non-invasive definition of cardiomyocyte necrosis. A trivalent arsenic peptide, GSAO (4-(N-(S-glutathionylacetyl)amino) phenylarsonous acid), is capable of binding to intracellular dithiol molecules such as HSP90 and filamin-A. Since GSAO is membrane impermeable and dithiol molecules abundantly present intracellularly, we propose that myocardial localization would represent sarcolemmal disruption or necrotic cell death. In rabbit and mouse models of myocardial infarction and post-infarct heart failure, we employed In-111-labelled GSAO for noninvasive radionuclide molecular imaging. In-111-GSAO uptake was observed within the regions of apoptosis seeking agent-(99)mTc-Annexin A5 uptake, suggesting the colocalization of apoptotic and necrotic cell death processes. This research was supported by a research grant from the International Research Fund for Subsidy of Kyusyu University School of Medicine Alumni and the Banyu Fellowship Program sponsored by Banyu Life Science Foundation International to N. Tahara, and research grants from the foundation ``De Drie Lichten´´ and the Dutch Heart Association (Dr. E. Dekker student Grant) to H. de Haas. DTPA-GSAO, DTPA-GSCA, Cy5.5 GSAO were supplied by Covidien Imaging Solutions. We thank H.H. Boersma for performing blood clearance excellent statistical support we thank E. Bagiella, supported by National Institutes of Health Grant UL1TR000067. Sí
Databáze: OpenAIRE