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Enhanced endothelin-converting enzyme immunoreactivity in early atherosclerosis
J A Grantham1, J A Schirger, E E Williamson
1Cardiorenal Research Laboratory, Mayo Clinic, Rochester, Minnesota 55905, USA.
Journal of Cardiovascular Pharmacology
|May 22, 1998
Summary
Local vascular Endothelin-1 (ET-1) increases in early atherosclerosis, driven by enhanced endothelin-converting enzyme (ECE) activity in neointimal cells. This local production, not circulating levels, is key to early disease progression.
Area of Science:
- Cardiovascular Biology
- Vascular Medicine
- Atherosclerosis Research
Background:
- Endothelin-1 (ET-1) is a potent vasoconstrictor and mitogen implicated in atherosclerosis.
- Plasma ET-1 levels rise in advanced atherosclerosis, but its local role in early stages is unclear.
- Endothelin-converting enzymes (ECEs) generate active ET-1 from its precursor.
Purpose of the Study:
- To investigate the local expression and distribution of ECE in experimental atherosclerosis.
- To determine if ECE is present in the neointima of atherosclerotic vessels.
- To correlate ECE presence with local ET-1 levels in early atherosclerosis.
Main Methods:
- Immunohistochemistry was used to detect ECE in aortic tissues.
- Radioimmunoassay (RIA) measured tissue and plasma ET-1 concentrations.
- Rabbits were fed a cholesterol-rich diet to induce experimental atherosclerosis.
Main Results:
- Vascular wall ET-1 levels were significantly higher in cholesterol-fed rabbits compared to controls.
- Circulating ET-1 concentrations did not differ between groups.
- ECE immunoreactivity was increased in atherosclerotic aortas, particularly in neointimal macrophages and smooth muscle cells.
Conclusions:
- Local vascular ET-1, but not circulating ET-1, is elevated in early experimental atherosclerosis.
- Increased ECE expression in atherosclerotic lesions suggests a role in local ET-1 generation.
- These findings highlight the importance of local ET-1 regulation in atherosclerosis development.