Endothelin-1-like immunoreactivity in human atherosclerotic coronary tissue: a detailed analysis of the cellular distribution of endothelin-1.
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, alpha-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 (11/27; 40 per cent) and MFBs (12/27; 44 per cent) in fibrous areas. Luminal endothelial cells (Ulex europeus agglutinin reaction-positive, UEA) exhibited strong ET-1-IR, whereas endothelial cells of intraplaque microvessels demonstrated inconsistent staining for ET-1. ISH revealed that ET 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.
Ihling
C
C
Department of Pathology, University of Freiburg, Germany.
Göbel
H R
HR
Lippoldt
A
A
Wessels
S
S
Paul
M
M
Schaefer
H E
HE
Zeiher
A M
AM
D001161:Arteriosclerosis / Q000378:metabolism*; D016232:Endothelins / Q000235:genetics / Q000378:metabolism*; D005263:Femoral Artery / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008264:Macrophages / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics
D016232:Endothelins; D012333:RNA, Messenger