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Updated: Aug 21, 2026

Quantitative Analysis and Characterization of Atherosclerotic Lesions in the Murine Aortic Sinus
Published on: December 8, 2013
Characterization of apoptotic macrophages in atheromatous tissue of humans and heritable hyperlipidemic rabbits
R Kinscherf1, M Wagner, H Kamencic
1Department of Anatomy and Cell Biology III, University of Heidelberg, Germany. Ralf.Kinscherf@urz.uni-heidelberg.de
Abstract:
Apoptotic macrophages are regularly found in atherosclerotic plaques indicating programmed cell death as one of their regulatory controls. The objective of this study was to characterize in more detail apoptotic macrophages in atherosclerotic lesions of humans and heritable hyperlipidemic (HHL) rabbits. Macrophages were immunohistochemically analyzed using antibodies directed against alphaMbeta2-integrins (CD11b/CD18), CD44, major histocompatibility complex (MHC) class I and II, inducible nitric oxide synthase (iNOS), manganese superoxide dismutase (MnSOD), tumor necrosis factor alpha (TNFalpha), p53, c-jun/AP-1 and rabbit macrophages (RAM-11) and the TUNEL (TdT-mediated dUTP nick end labeling) technique. Colocalization studies of human atherosclerotic carotid and aortic tissue showed apoptotic plaque macrophages also being MnSOD-, alphaMbeta2-integrin-, CD44-, MHC class I- and II-, iNOS-, TNFalpha- and p53-immunoreactive. Similar results occurred in atherosclerotic aortas of HHL rabbits. Computer-assisted morphometric analyses revealed a positive correlation of the area density of MnSOD-immunoreactive macrophages with those of alphaMbeta2-integrin- and CD44-immunoreactive ones, but not with those of MHC class I- and II- as well as of RAM-11-immunoreactive macrophages. We conclude that apoptotic macrophages located in atherosclerotic vessel wall are activated, antigen-presenting, integrin-expressing and oxidatively stressed cells. Since all these processes have been demonstrated to cause apoptosis of macrophages in vitro, we propose their potency accelerates the susceptibility of the macrophages to programmed cell death in atherosclerotic lesions.
Insights
Apoptotic macrophages in atherosclerosis are activated, oxidatively stressed, and express integrins, suggesting these factors accelerate their programmed cell death within lesions.
Area of Science:
- Cardiovascular Biology
- Immunology
- Cellular Pathology
Background:
- Apoptotic macrophages are prevalent in atherosclerotic plaques, indicating programmed cell death's role in disease regulation.
- Understanding the characteristics of these apoptotic macrophages is crucial for elucidating atherosclerosis pathogenesis.
Purpose of the Study:
- To comprehensively characterize apoptotic macrophages within human and heritable hyperlipidemic (HHL) rabbit atherosclerotic lesions.
- To investigate the molecular markers and cellular states associated with macrophage apoptosis in atherosclerosis.
Main Methods:
- Immunohistochemical analysis of human carotid/aortic and HHL rabbit aortic tissues using antibodies against CD11b/CD18, CD44, MHC class I/II, iNOS, MnSOD, TNFα, p53, c-jun/AP-1, RAM-11.
- TUNEL (TdT-mediated dUTP nick end labeling) technique to identify apoptotic cells.
- Computer-assisted morphometric analysis for quantitative correlation studies.
Main Results:
- Apoptotic macrophages in human and HHL rabbit lesions exhibited co-localization with markers for MnSOD, alphaMbeta2-integrin, CD44, MHC class I/II, iNOS, TNFα, and p53.
- Morphometric analysis revealed positive correlations between MnSOD-immunoreactive macrophages and alphaMbeta2-integrin/CD44-immunoreactive macrophages.
- No significant correlation was found between MnSOD-immunoreactive macrophages and MHC class I/II or RAM-11-immunoreactive macrophages.
Conclusions:
- Apoptotic macrophages in atherosclerotic lesions are characterized as activated, antigen-presenting, integrin-expressing, and oxidatively stressed.
- These cellular states, known to induce apoptosis in vitro, likely contribute to the susceptibility of macrophages to programmed cell death within atherosclerotic lesions.
- The findings highlight the complex role of macrophage apoptosis in the progression of atherosclerosis.
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