Cellular and immunologic features of carotid artery disease in man and experimental animal models
1Department of Surgery, Gothenburg University, Sahlgren's Hospital, Sweden.
Insights
Comparing experimental models of atherosclerosis and intimal hyperplasia reveals distinct cellular compositions. Macrophages dominate human plaques and cholesterol-fed rabbit lesions, while balloon-injured rat lesions primarily feature smooth muscle cells, offering insights into disease pathogenesis.
Area of Science:
- Cardiovascular Biology
- Immunohistochemistry
- Pathogenesis Research
Background:
- Atherosclerosis and post-surgical intimal hyperplasia pathogenesis require understanding lesion cellularity.
- Immunohistochemical techniques are crucial for analyzing lesion cell composition.
Purpose of the Study:
- Compare cellular makeup of human atherosclerotic plaques with experimental models.
- Evaluate suitability of experimental models for studying specific aspects of human vascular disease.
Main Methods:
- Immunohistochemistry used to identify cell types in human carotid endarterectomy specimens.
- Comparison with lesions induced in rats (mechanical injury) and rabbits (cholesterol feeding).
- Antibodies to cell-specific antigens and enzyme-conjugated second antibodies for visualization.
Main Results:
- Human plaques and cholesterol-fed rabbit lesions show macrophage dominance in lipid core.
- Rat balloon catheter injury model predominantly features vascular smooth muscle cells with some inflammatory infiltrate.
- Human lesions have higher proportions of T lymphocytes and macrophages than experimental models.
- Class II major histocompatibility antigens induced on cells in all lesion types, suggesting T lymphocyte activation.
Conclusions:
- Experimental models partially mimic human atherosclerosis and intimal hyperplasia.
- The choice of experimental model depends on the specific research question.
- Balloon catheter model is suitable for studying intimal hyperplasia and fibrous cap formation.
Abstract:
A better understanding of the pathogenesis of atherosclerosis and of post surgical intimal hyperplasia can be obtained by analysis of the cellular composition of the lesions using immunohistochemical techniques. In the present study, we have compared human atherosclerotic plaques obtained as endarterectomy specimens from the carotid artery, with lesions induced by mechanical injury and cholesterol feeding in rats and rabbits. Antibodies to cell type-specific antigens were used to identify cells, and visualisation was with enzyme-conjugated second antibodies. Our data show that the lipid core region of the human plaque is dominated by macrophages. Such cells also dominate the lesions of cholesterol-fed rabbits. In contrast, intimal lesions induced by balloon catheters in rats consist almost entirely of vascular smooth muscle cells, with a small inflammatory infiltrate of monocytes and T lymphocytes. This situation resembles that in the fibrous cap region of the human plaque. However, the human lesion contains a much higher proportion of T lymphocytes and macrophages than the experimental one. In all types of lesions, class II major histocompatibility antigens were induced on the cells, suggesting that an immune reaction with activation of T lymphocytes may be taking place. Finally, different subpopulations of smooth muscle cells were observed, possibly representing different degrees of differentiation or a response to immune mediators. In conclusion, our studies demonstrate that different experimental models resemble the human disease in various aspects. The choice of experimental model will therefore depend on the problem to be studied. The balloon catheter model should be ideally suited for studies of intimal hyperplasia after surgery and also for studies of fibrous cap formation.(ABSTRACT TRUNCATED AT 250 WORDS)
