TY  - JOUR
AB  - Cardiovascular disease remains the most frequent cause of death worldwide. Atherosclerosis, an underlying cause of cardiovascular disease, is an inflammatory disorder associated with endothelial dysfunction. The endothelin system plays a crucial role in the pathogenesis of endothelial dysfunction and is involved in the development of atherosclerosis. We aimed to reveal the expression levels of the endothelin-A receptor (ETAR) in the course of atherogenesis to reveal possible time frames for targeted imaging and interventions. We used the ApoE−/− mice model and human specimens and evaluated ETAR expression by quantitative rtPCR (qPCR), histology and fluorescence molecular imaging. We found a significant upregulation of ETAR after 22 weeks of high-fat diet in the aortae of ApoE−/− mice. With regard to translation to human disease, we applied the fluorescent probe to fresh explants of human carotid and femoral artery specimens. The findings were correlated with qPCR and histology. While ETAR is upregulated during the progression of early atherosclerosis in the ApoE−/− mouse model, we found that ETAR expression is substantially reduced in advanced human atherosclerotic plaques. Moreover, those expression changes were clearly depicted by fluorescence imaging using our in-house designed ETAR-Cy 5.5 probe confirming its specificity and potential use in future studies.
AU  - Stölting, Miriam
AU  - Geyer, Christiane
AU  - Helfen, Anne
AU  - Hahnenkamp, Anke
AU  - Usai, Marco V.
AU  - Wardelmann, Eva
AU  - Kuhlmann, Michael Theodor
AU  - Wildgruber, Moritz
AU  - Höltke, Carsten
DA  - 2020-11-26
DO  - 10.17879/34019679593
KW  - atherosclerosis
KW  - endothelin system
KW  - molecular imaging
KW  - ApoE-KnockOut
KW  - carotid endarterectomy
KW  - fluorescence imaging
KW  - endothelin receptor expression
LA  - eng
N1  - Biomedicines 8 (2020) 12, 538, 1-15
N1  - Finanziert durch den Open-Access-Publikationsfonds der Westfälischen Wilhelms-Universität Münster (WWU Münster).
N1  - Förderer: Deutsche Forschungsgemeinschaft / Projektnummer: 412846220
N1  - Funding organisation: Deutsche Forschungsgemeinschaft / Project number: 412846220
PY  - 2020-11-26
TI  - Monitoring Endothelin-A Receptor Expression during the Progression of Atherosclerosis
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:6-04019502604
Y2  - 2024-11-22T05:37:35
ER  -