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Updated: Feb 11, 2026

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Published on: January 15, 2022
Leukocyte Dynamics during the Evolution of Human Coronary Atherosclerosis: Conclusions from a Sevenfold,
Melissa Zuiderwijk1, Marlieke Geerts1, Connie J van Rhijn1
1Einthoven Laboratory for Cardiovascular Medicine, Division of Vascular Surgery, Department of Surgery, Leiden University Medical Center, Leiden.
Insights
This study reveals that macrophages and T cells increase with atherosclerosis progression in human coronaries. B cells appear during plaque destabilization, while neutrophils indicate rupture, and CD36 is not key for foam cell formation.
Area of Science:
- Cardiovascular Biology
- Immunology
- Pathology
Background:
- Atherosclerosis is a chronic inflammatory disease.
- Understanding leukocyte dynamics is crucial for disease management.
- Current methods for analyzing atherosclerotic lesions are complex.
Purpose of the Study:
- To develop a comprehensive staining protocol for human coronary atherosclerosis.
- To simultaneously assess leukocyte populations, vascularization, and CD36 expression.
- To elucidate the role of different immune cells in plaque progression and destabilization.
Main Methods:
- A novel sevenfold staining protocol was applied to human coronary arteries.
- The method allowed simultaneous evaluation of macrophages, T cells, B cells, neutrophils, mast cells, vascularization, and CD36.
- Lesions were analyzed across the full spectrum of atherosclerotic disease.
Main Results:
- Macrophage and T-cell abundance progressively increased with plaque progression.
- B cells were found exclusively in adventitial follicles during plaque destabilization.
- Neutrophils were associated with hemorrhage in ruptured plaques; CD36 was not identified as a key foam cell factor.
Conclusions:
- The developed protocol effectively characterizes immune cell infiltration in atherosclerosis.
- Macrophage and T-cell accumulation correlates with disease progression and neoatherosclerosis.
- Plaque healing involves reduced inflammation, but atherosclerosis may recur.
Abstract:
Atherosclerosis is a complex process with strong inflammatory component. We developed a straightforward sevenfold staining protocol for simultaneous assessment of dominant leukocyte classes, vascularization, and expression of the putative foam cell maker CD36. The method was applied on human coronaries covering the full spectrum of atherosclerotic disease. Results confirm the progressive association of macrophages and T cells with the process and a global presence of mast cells. B cells are exclusively present in adventitial follicles that accompany the process plaque destabilization (thin cap and ruptured lesions) and are otherwise absent. Neutrophils are only present as part of the hemorrhage that accompanies plaque rupture. This study does not classify CD36 as a key factor in foam cell formation. Observed macrophage accumulation in the neointima of stabilized fibrous calcified plaques is consistent with a process of neoatherosclerosis. This study on human coronaries shows a progressive association of macrophage and T-cell abundance with plaque progression. Follicle-like structures are transiently present during the process of plaque destabilization. Plaque healing is accompanied by cessation of the inflammatory response but followed by a new cycle of atherosclerosis.
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