ENDOTHELIN-1-LIKE IMMUNOREACTIVITY IN HUMAN ATHEROSCLEROTIC CORONARY TISSUE:A DETAILED ANALYSIS OF THE CELLULAR DISTRIBUTION OF ENDOTHELIN-1
✍ Scribed by IHLING, CHRISTIAN; GÖBEL, HEIKE R.; LIPPOLDT, ANDREA; WESSELS, SABINE; PAUL, MARTIN; SCHAEFER, HANS E.; ZEIHER, ANDREAS M.
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- English
- Weight
- 871 KB
- Volume
- 179
- Category
- Article
- ISSN
- 0022-3417
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✦ Synopsis
Endothelin (ET) is a very potent vasoconstrictor peptide, which was originally reported to be produced by endothelial cells and to act locally in a paracrine fashion to regulate vascular tone. Recent studies have demonstrated that endothelin-1 (ET-1) not only is produced by endothelial cells, but is also present in non-endothelial cells of atherosclerotic lesions. The present study was therefore designed to characterize the cell type and distribution of ET-expressing cells in different areas of human atherosclerotic coronary plaques, obtained by directional atherectomy of 30 patients. In addition, ET-1 messenger RNA (mRNA) distribution was studied in human atherosclerotic plaque tissue by in situ hybridization (ISH). The strongest ET-1-like immunoreactivity (ET-1-IR) was present in all cell-rich areas of 27 plaques. In fibrotic areas of 27 tissue samples, ET-1-IR was found in 44 per cent (12/27). ET expression was most prevalent in foamy macrophages (MPs, HAM 56-positive) and myofibroblasts (MFBs, a-actin-positive) in the vicinity of necrotic areas with signs of previous intraplaque haemorrhage. By contrast, ET-1-IR was weak and inconsistently found in MPs (11127; 40 per cent) and MFBs (12/27; 44 per cent) in fibrous areas. Luminal endothelial cells (Ulex euvopeus agglutinin reaction-positive, UEA) exhibited strong ET-1-IR, whereas endothelial cells of intraplaque microvessels demonstrated inconsistent staining for ET-1. ISH revealed that E T mRNA is produced locally in intimal MPs showing strong ET-1-IR. These findings demonstrate that ET-1 is produced by human MPs, the principal inflammatory cell type in atherosclerosis, suggesting a role for ET-1 in the chronic inflammation associated with complicated atherosclerosis.