Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content.
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OBJECTIVE: To assess the size of the lipid pool and the number of smooth muscle cells and monocyte/macrophages in human aortic plaques that were intact and to compare the results with those in aortic plaques undergoing ulceration and thrombosis. DESIGN: The lipid pool was measured as a percentage of the total cross sectional area of the plaque. Immunohistochemistry was used to identify cell types (monocytes/macrophages (M phi) by EBM11 and HAM56, smooth muscle cells by alpha actin). The area of the tissue occupied by each cell type was measured by quantitative microscopy in the peripheral (shoulder) area of the plaque and the plaque cap. Absolute counts of each cell type were expressed as the ratio of SMC:M phi. MATERIAL: Aortas were obtained at necropsy from men aged less than 69 years who died suddenly (within 6 hours of the onset of symptoms) of ischaemic heart disease. 155 plaques from 13 aortas were studied. Four aortas showed intact plaques only (group A, n = 31). Nine aortas showed both intact plaques (group B, n = 79) and plaques that were undergoing thrombosis (group C, n = 45). RESULTS: In 41 (91.1%) of the 45 plaques undergoing thrombosis (group C) lipid pools occupied more than 40% of the cross sectional area of the plaque. Only 12 (10.9%) of the 110 intact plaques (groups A + B) had lipid pools of this size. The mean size of the lipid pool in plaques of groups A, B, and C was 12.7%, 27.3% and 56.7% respectively. Compared with intact plaques those undergoing thrombosis contained a smaller volume of smooth muscle cells (2.8% v 11.8%) and a larger volume of monocyte/macrophages (13.7% v 2.9%) in the plaque cap. The ratio of the number of smooth muscle cells to monocytes/macrophages was 7.8 in group A plaques, 4.1 in group B plaques, and 1.0 in group C plaques. This gradient was the result of an absolute increase in monocyte/macrophages and an absolute decrease in smooth muscle cells. CONCLUSIONS: In the aorta ulceration and thrombosis were characteristic of plaques with a high proportion of their volume occupied by extracellular lipid, and in which there was a shift toward a preponderance of monocyte/macrophages compared with smooth muscle cells in the cap.
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The integrity of the fibrous cap, comprising mostly αSMA-positive cells and associated ECM, is critical to stabilise and protect plaques from rupture.
“detailed post-mortem analyses of culprit plaques in sudden cardiac death established that the integrity of the fibrous cap, comprising mostly α SMA-positive cells and associated extracellular matrix (ECM), is critical to stabilise and protect plaques from rupture, a major cause of the clinical sequalae of atherosclerosis 142,163,168 .”
From Vascular smooth muscle cells in atherosclerosis (2019) · cites this paper as [142]
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- Authors
- Davies, M. J., Richardson, P. D., Woolf, N., Katz, D. R., & Mann, J.
- Affiliations
- St George's, University of London (GB)
- Venue
- Heart
- Publisher
- BMJ
- Published
- 1993-05-01
- Volume
- 69
- Issue
- 5
- Pages
- 377-381
- ISSN
- 1355-6037 (ISSN-L)
- PMC
- PMC1025095
- OpenAlex
- W2026856116
- Cited by
- 1,127
- References
- 29
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 12 · 2023: 14 · 2022: 12 · 2021: 18 · 2020: 25 · 2019: 14 · 2018: 23 · 2017: 20 · 2016: 27 · 2015: 37 · 2014: 45 · 2013: 36 · 2012: 37
- FWCI
- 10.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Heart (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Aortic Thrombus and Embolism
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cerebrovascular and Carotid Artery Diseases
- Keywords
- atherosclerosis, aortic plaque, thrombosis, plaque ulceration, lipid pool, extracellular lipids, macrophages, smooth muscle cells, plaque vulnerability, sudden cardiac death, ischemic heart disease, plaque composition, plaque rupture risk, plaque regression
- MeSH terms
- Aged, Aorta, Arteriosclerosis, Cell Count, Humans, Immunohistochemistry, Lipids, Macrophages, Male, Muscle, Smooth, Vascular, Risk Factors, Thrombosis
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