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Topography of immune cell infiltration in different stages of coronary atherosclerosis revealed by multiplex immunohistochemistry.


ABSTRACT:

Background

Aim of this study was to investigate immune cells and subsets in different stages of human coronary artery disease with a novel multiplex immunohistochemistry (mIHC) technique.

Methods

Human left anterior descending coronary artery specimens were analyzed: eccentric intimal thickening (N = 11), pathological intimal thickening (N = 10), fibroatheroma (N = 9), and fibrous plaque (N = 9). Eccentric intimal thickening was considered normal, and pathological intimal thickening, fibroatheroma, and fibrous plaque were considered diseased coronary arteries. Two mIHC panels, consisting of six and five primary antibodies, autofluoresence, and DAPI, were used to detect adaptive and innate immune cells. Via semi-automated analysis, (sub)types of immune cells in whole plaques and specific plaque regions were quantified.

Results

Increased numbers of CD3+ T cells (P < 0.001), CD20+ B cells (P = 0.013), CD68+ macrophages (P = 0.003), CD15+ neutrophils (P = 0.017), and CD31+ endothelial cells (P = 0.024) were identified in intimas of diseased coronary arteries compared to normal. Subset analyses of T cells and macrophages showed that diseased coronary arteries contained an abundance of CD3+CD8- non-cytotoxic T cells and CD68+CD206- non-M2-like macrophages. Proportions of CD3+CD45RO+ memory T cells were similar to normal coronary arteries. Among pathological intimal thickening, fibroatheroma, and fibrous plaque, all immune cell numbers and subsets were similar.

Conclusions

The type of immune response does not differ substantially between different stages of plaque development and may provide context for mechanistic research into immune cell function in atherosclerosis. We provide the first comprehensive map of immune cell subtypes across plaque types in coronary arteries demonstrating the potential of mIHC for vascular research.

SUBMITTER: Cortenbach KRG 

PROVIDER: S-EPMC9938475 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Topography of immune cell infiltration in different stages of coronary atherosclerosis revealed by multiplex immunohistochemistry.

Cortenbach Kimberley R G KRG   Morales Cano Daniel D   Meek Jelena J   Gorris Mark A J MAJ   Staal Alexander H J AHJ   Srinivas Mangala M   Jolanda M de Vries I I   Fog Bentzon Jacob J   van Kimmenade Roland R J RRJ  

International journal of cardiology. Heart & vasculature 20220824


<h4>Background</h4>Aim of this study was to investigate immune cells and subsets in different stages of human coronary artery disease with a novel multiplex immunohistochemistry (mIHC) technique.<h4>Methods</h4>Human left anterior descending coronary artery specimens were analyzed: eccentric intimal thickening (N = 11), pathological intimal thickening (N = 10), fibroatheroma (N = 9), and fibrous plaque (N = 9). Eccentric intimal thickening was considered normal, and pathological intimal thickeni  ...[more]

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