A molecular intravascular ultrasound contrast agent allows detection of activated platelets on the surface of symptomatic human plaques
| Autor: | Peter Bronsert, Felix Guenther, Karlheinz Peter, Mara Kramer, Patricia Plaza-Heck, Fabian Meixner, Andreas Zirlik, Peter Stachon, Jochen Reinöhl, Irene Neudorfer, Ingo Hilgendorf, Ralf Birkemeyer, Christoph Bode, Beat A. Kaufmann, Alexander Maier, Timo Heidt, Constantin von zur Mühlen |
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| Rok vydání: | 2017 |
| Předmět: |
Blood Platelets
Pathology medicine.medical_specialty medicine.medical_treatment Contrast Media 030204 cardiovascular system & hematology Ligands 030218 nuclear medicine & medical imaging 03 medical and health sciences 0302 clinical medicine Intravascular ultrasound medicine Humans Platelet cardiovascular diseases Platelet activation Thrombus Ultrasonography Interventional Ultrasonography Endarterectomy Endarterectomy Carotid Binding Sites Microbubbles medicine.diagnostic_test Chemistry Thrombosis Atherosclerosis Platelet Activation medicine.disease Plaque Atherosclerotic Microscopy Fluorescence Immunoglobulin G cardiovascular system Molecular imaging Cardiology and Cardiovascular Medicine Selectin |
| Zdroj: | Atherosclerosis. 267:68-77 |
| ISSN: | 0021-9150 |
| Popis: | Background and aims Activated platelets are amongst the most attractive imaging targets in atherosclerosis due to their important role in early processes of atherogenesis and thrombus formation. We developed a molecular intravascular ultrasound (IVUS) approach to detect activated platelets ex vivo on the surface of human plaques, using an IVUS system applied in clinical routine. Methods Human carotid endarterectomy specimens were obtained directly from the operating room and exposed to artificial arterial flow conditions for incubation with the contrast agent. This consists of microbubbles (MB), which are linked to an antibody against the ligand induced binding site (LIBS) of the activated platelet glycoprotein IIb/IIa, and a sialyl Lewis polymer (SL), which mediates binding to selectins (LIBS-SL-MB). IVUS was performed pre and post incubation with LIBS-SL-MB and after rinsing with PBS. In comparison, IVUS was performed pre and post incubation with MBs linked to an unspecific control antibody and a dysfunctional polymer (control-MB). All imaging results were correlated to histology findings. Results IVUS imaging showed a high signal enhancement after administration of LIBS-SL-MB. After rinsing with PBS, the signal enhancement remained stable. Immunofluorescence and immunohistochemistry confirmed significant binding of microbubbles to thrombi on the plaque surface. Moreover, thrombus size and number of bound MBs correlated well. Conclusions LIBS-SL-MB allows ex vivo IVUS imaging of even small numbers of activated platelets on the surface of human carotid endarterectomy specimens. This diagnostic approach could deliver valuable additional information for risk stratification of atherosclerotic plaques, especially since we apply a clinically well-established IVUS imaging system. |
| Databáze: | OpenAIRE |
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