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Published on: September 26, 2018
Monitoring Endothelin-A Receptor Expression during the Progression of Atherosclerosis
Miriam Stölting1, Christiane Geyer1, Anne Helfen1
1Clinic for Radiology, University Hospital Münster, D-48149 Münster, Germany.
Insights
Endothelin-A receptor (ETAR) expression increases in early atherosclerosis in mice but decreases in advanced human plaques. This finding highlights potential differences in ETAR targeting for cardiovascular disease interventions.
Area of Science:
- Cardiovascular Research
- Molecular Imaging
- Atherosclerosis Pathogenesis
Background:
- Cardiovascular disease is a leading global cause of death, with atherosclerosis as a primary driver.
- Atherosclerosis is an inflammatory condition linked to endothelial dysfunction, where the endothelin system plays a key role.
- Understanding endothelin-A receptor (ETAR) expression is crucial for developing targeted therapies for atherosclerosis.
Purpose of the Study:
- To investigate the expression levels of endothelin-A receptor (ETAR) during atherogenesis.
- To identify potential time windows for ETAR-targeted imaging and therapeutic interventions.
- To compare ETAR expression in a mouse model with human atherosclerotic tissues.
Main Methods:
- Utilized the ApoE-/- mouse model fed a high-fat diet.
- Evaluated ETAR expression using quantitative rtPCR (qPCR), histology, and fluorescence molecular imaging.
- Applied an in-house designed ETAR-Cy 5.5 fluorescent probe to mouse aortae and human carotid/femoral artery explants.
Main Results:
- Significant upregulation of ETAR was observed in the aortae of ApoE-/- mice after 22 weeks on a high-fat diet.
- In contrast, ETAR expression was substantially reduced in advanced human atherosclerotic plaques.
- Fluorescence imaging effectively depicted these expression changes, confirming the probe's specificity.
Conclusions:
- ETAR expression dynamics differ between early experimental atherosclerosis and advanced human disease.
- Findings suggest that ETAR-targeted imaging and interventions may require careful consideration of disease stage.
- The developed ETAR-Cy 5.5 probe shows potential for future studies in atherosclerosis research.
Abstract:
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.
