Academic Journal
Gene expression levels of matrix metalloproteinases in human atherosclerotic plaques and evaluation of radiolabeled inhibitors as imaging agents for plaque vulnerability.
| العنوان: | Gene expression levels of matrix metalloproteinases in human atherosclerotic plaques and evaluation of radiolabeled inhibitors as imaging agents for plaque vulnerability. |
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| المؤلفون: | Müller, Adrienne, Krämer, Stefanie D, Meletta, Romana, Beck, Katharina, Selivanova, Svetlana V, Rancic, Zoran, Kaufmann, Philipp A, Vos, Bernhard, Meding, Jörg, Stellfeld, Timo, Heinrich, Tobias K, Bauser, Marcus, Hütter, Joachim, Dinkelborg, Ludger M, Schibli, Roger, Ametamey, Simon M |
| المصدر: | Müller, Adrienne; Krämer, Stefanie D; Meletta, Romana; Beck, Katharina; Selivanova, Svetlana V; Rancic, Zoran; Kaufmann, Philipp A; Vos, Bernhard; Meding, Jörg; Stellfeld, Timo; Heinrich, Tobias K; Bauser, Marcus; Hütter, Joachim; Dinkelborg, Ludger M; Schibli, Roger; Ametamey, Simon M (2014). Gene expression levels of matrix metalloproteinases in human atherosclerotic plaques and evaluation of radiolabeled inhibitors as imaging agents for plaque vulnerability. Nuclear medicine and biology, 41(7):562-569. |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2014 |
| المجموعة: | University of Zurich (UZH): ZORA (Zurich Open Repository and Archive |
| مصطلحات موضوعية: | Clinic for Nuclear Medicine, 610 Medicine & health |
| الوصف: | INTRODUCTION Atherosclerotic plaque rupture is the primary cause for myocardial infarction and stroke. During plaque progression macrophages and mast cells secrete matrix-degrading proteolytic enzymes, such as matrix metalloproteinases (MMPs). We studied levels of MMPs and tissue inhibitor of metalloproteinases-3 (TIMP-3) in relation to the characteristics of carotid plaques. We evaluated in vitro two radiolabeled probes targeting active MMPs towards non-invasive imaging of rupture-prone plaques. METHODS Human carotid plaques obtained from endarterectomy were classified into stable and vulnerable by visual and histological analysis. MMP-1, MMP-2, MMP-8, MMP-9, MMP-10, MMP-12, MMP-14, TIMP-3, and CD68 levels were investigated by quantitative polymerase chain reaction. Immunohistochemistry was used to localize MMP-2 and MMP-9 with respect to CD68-expressing macrophages. Western blotting was applied to detect their active forms. A fluorine-18-labeled MMP-2/MMP-9 inhibitor and a tritiated selective MMP-9 inhibitor were evaluated by in vitro autoradiography as potential lead structures for non-invasive imaging. RESULTS Gene expression levels of all MMPs and CD68 were elevated in plaques. MMP-1, MMP-9, MMP-12 and MMP-14 were significantly higher in vulnerable than stable plaques. TIMP-3 expression was highest in stable and low in vulnerable plaques. Immunohistochemistry revealed intensive staining of MMP-9 in vulnerable plaques. Western blotting confirmed presence of the active form in plaque lysates. In vitro autoradiography showed binding of both inhibitors to stable and vulnerable plaques. CONCLUSIONS MMPs differed in their expression patterns among plaque phenotypes, providing possible imaging targets. The two tested MMP-2/MMP-9 and MMP-9 inhibitors may be useful to detect atherosclerotic plaques, but not the vulnerable lesions selectively. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 0969-8051 |
| Relation: | https://www.zora.uzh.ch/98377; info:pmid/24853402; urn:issn:0969-8051 |
| DOI: | 10.1016/j.nucmedbio.2014.04.085 |
| الاتاحة: | https://www.zora.uzh.ch/id/eprint/98377/ https://www.zora.uzh.ch/98377 https://doi.org/10.1016/j.nucmedbio.2014.04.085 |
| Rights: | info:eu-repo/semantics/closedAccess |
| رقم الانضمام: | edsbas.FF44D91B |
| قاعدة البيانات: | BASE |
| تدمد: | 09698051 |
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| DOI: | 10.1016/j.nucmedbio.2014.04.085 |