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The endothelium of advanced arteriosclerotic plaques in humans
1Institute of Pathology, Heinrich-Heine University, Düsseldorf, FRG.
Insights
Endothelial cells (ECs) in advanced atherosclerotic plaques show altered properties without denudation. These changes, including giant ECs and immune activation, may contribute to plaque growth and EC dysfunction in arteriosclerosis.
Area of Science:
- Vascular Biology
- Pathology
- Cell Biology
Background:
- Atherosclerosis involves changes in artery walls, particularly endothelial cells (ECs).
- Understanding ECs in advanced plaques is crucial for elucidating arteriosclerosis pathogenesis.
Purpose of the Study:
- To investigate the functional morphology of endothelial cells (ECs) in advanced human atherosclerotic plaques.
- To identify alterations in ECs and their potential role in plaque development.
Main Methods:
- Studied carotid endarterectomy and explanted coronary artery specimens.
- Utilized light microscopy, electron microscopy, and double immunofluorescence for EC identification and characterization.
Main Results:
- Endothelial layer was mostly intact, with patterns reflecting local blood flow.
- Frequent presence of large (giant) ECs, suggesting senescence due to disturbed flow.
- ECs showed signs of activation, including organelle hyperplasia and expression of class II antigens (e.g., HLA-DR).
- Increased myo-endothelial contacts with smooth muscle cells were observed.
Conclusions:
- Altered ECs in advanced plaques exhibit changed properties without denudation.
- EC activation and senescence may contribute to plaque growth and EC dysfunction in arteriosclerosis.
- Novel EC-smooth muscle cell interactions may play a role in lesion development.
Abstract:
The functional morphology of the endothelial cells (ECs) covering advanced but uncomplicated sclerotic plaques in humans was studied in carotid endarterectomy specimens and in coronary arteries from hearts explanted because of advanced ischemic heart disease. The endothelial layer was nearly always intact, and the endothelial patterns reflected the anticipated local flow patterns along the narrowed arteries, with the majority of flow irregularities downstream from the stenosis. Large (giant) ECs (defined as ECs with a surface area of greater than or equal to 800 microns 2) were frequently found on the plaque surface, probably indicating accelerated EC senescence attributable to sustained nondenuding injury in the region of disturbed flow. Ultrastructurally, activation of ECs with hyperplasia of organelles was frequent. In addition, as a sign of immunological activation, about 5% of ECs express class II antigens (HLA-DR and rarely focal HLA-DQ), as demonstrated by double immunofluorescence with von Willebrand factor to identify the ECs. EC activation may be responsible for adherence to the intact luminal surface by activated platelets and monocytes, which were always present (in contrast with nonsclerotic artery segments). Furthermore, an increase in myo-endothelial contacts to subendothelial modified smooth muscle cells was a regular feature of the sclerotic lesions; this feature represents an unknown process of EC and smooth muscle cell interaction in the sclerotic lesion and may be a compensatory process for EC control of smooth muscle cell proliferation. In advanced plaques the ECs are altered without denudation but with changed properties, which may contribute to plaque growth and which are consistent with the postulated EC dysfunction in the pathogenesis of arteriosclerotic lesions.