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Procoagulant activity expression by macrophages from atheromatous vascular plaques
P G Tipping1, J Malliaros, S R Holdsworth
1Monash University Department of Medicine, Prince Henry's Hospital, Melbourne, Australia.
Atherosclerosis
|October 1, 1989
Summary
Macrophages in carotid artery plaques exhibit heightened procoagulant activity (PCA), significantly exceeding that of blood monocytes and macrophages from other atherosclerotic lesions. This enhanced PCA in carotid macrophages may drive thrombus formation on ulcerated plaques, contributing to stroke risk.
Area of Science:
- Cardiovascular Biology
- Immunology
- Thrombosis Research
Background:
- Atherosclerotic carotid artery disease can lead to embolization of thrombi from ulcerated plaques, causing significant morbidity.
- The mechanisms controlling thrombus formation on these atherosclerotic lesions are not fully understood.
- Macrophages within plaques are investigated for their role in local fibrin deposition.
Purpose of the Study:
- To assess the procoagulant activity (PCA) of macrophages isolated from atherosclerotic carotid plaques.
- To compare the PCA of carotid plaque macrophages with macrophages from other atherosclerotic lesions and blood monocytes.
- To investigate the factors contributing to the PCA of carotid plaque macrophages.
Main Methods:
- Isolation of macrophages from carotid endarterectomy plaques and other atherosclerotic lesions, as well as blood monocytes.
- Measurement of procoagulant activity (PCA) of isolated cells.
- Functional assays including inhibition studies with anti-tissue factor antibody.
- Immunohistochemical analysis of plaque tissue for tissue factor expression.
Main Results:
- Carotid plaque macrophages demonstrated significantly higher PCA (8.6 +/- 4.1 mU/10(6) cells) compared to macrophages from non-carotid lesions (0.35 +/- 0.20 mU/10(6) cells) and blood monocytes.
- PCA of carotid plaque macrophages was markedly elevated in patients with recent emboli (16.1 +/- 8.4 mU/10(6) cells) versus asymptomatic patients (2.4 +/- 0.8 mU/10(6) cells).
- Carotid macrophage PCA was dependent on factors V and VII, inhibited by anti-tissue factor antibody, and associated with abundant tissue factor in macrophages.
Conclusions:
- Macrophages within carotid artery plaques possess augmented procoagulant activity compared to blood monocytes and macrophages from other atherosclerotic sites.
- These findings indicate that carotid plaque macrophages are activated and contribute to local thrombus formation.
- The elevated macrophage PCA is a potential mechanism driving thrombus formation on ulcerated carotid plaques, increasing stroke risk.