The role of myeloperoxidase and collagen–elastin scaffold in development of unstable atherosclerotic plaques in humans

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Abstract

Background: Some current evidence suggest that myeloperoxidase may participate in the pathogenesis of atherosclerosis. However, its role in the development of unstable atherosclerotic lesions in humans and effects on a collagen-elastin scaffold of the vascular wall are poorly understood.

Aim: This study aimed to compare the immunohistochemical assays of myeloperoxidase, smooth muscle cells, and elastic and collagen fibers in various types of human atherosclerotic lesions.

Methods: Histology and immunohistochemistry tests were performed on autopsy samples obtained from 21 patients who died from acute cardiovascular failure caused by atherosclerosis. Segments of the aorta (from the arch, thoracic, and abdominal regions), coronary arteries, and the basilar artery were examined. A total of 50 tissue samples were included. We used a highly sensitive, two-step avidin–biotin assay technique to detect myeloperoxidase expression in various types of atherosclerotic vascular wall lesions.

Results: Intracellular myeloperoxidase location was detected in the intima of unstable atherosclerotic plaques, and its amount increased as the lesions progressed. However, unstable plaques showed a significant decrease in smooth muscle cells and destruction of the collagen–elastin scaffold. This was accompanied by the degradation of elastic and collagen fibers, as well as the rupture of the plaque cap.

Conclusion: It is hypothesized that the production of myeloperoxidase by mononuclear cells negatively affects human smooth muscle cells by promoting apoptosis and inhibiting the synthesis of elastic and collagen fibers in the vascular wall. This may destabilize atherosclerotic lesions.

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About the authors

Peter V. Pigarevsky

Institute of Experimental Medicine

Author for correspondence.
Email: pigarevsky@mail.ru
ORCID iD: 0000-0002-5906-6771
SPIN-code: 8636-4271

Dr. Sci. (Biology)

Russian Federation, 12 Akademika Pavlova st, Saint Petersburg, 197376

Svetlana V. Maltseva

Institute of Experimental Medicine

Email: moon25@rambler.ru
ORCID iD: 0000-0001-7680-8485
SPIN-code: 8367-9096

Cand. Sci. (Biology)

Russian Federation, 12 Akademika Pavlova st, Saint Petersburg, 197376

Vlada A. Snegova

Institute of Experimental Medicine

Email: biolaber@inbox.ru
ORCID iD: 0000-0002-9925-2886
SPIN-code: 8088-4446

Cand. Sci. (Biology)

Russian Federation, 12 Akademika Pavlova st, Saint Petersburg, 197376

Natalya G. Davydova

Institute of Experimental Medicine; North-Western State Medical University named after I.I. Mechnikov

Email: tatashaspb@yandex.ru
ORCID iD: 0000-0002-4522-6789
SPIN-code: 4761-3575

MD, Cand. Sci. (Medicine)

Russian Federation, 12 Akademika Pavlova st, Saint Petersburg, 197376; Saint Petersburg

Olga G. Yakovleva

Institute of Experimental Medicine

Email: emalonett@yandex.ru
ORCID iD: 0000-0002-6248-9468
SPIN-code: 4963-5064
Russian Federation, 12 Akademika Pavlova st, Saint Petersburg, 197376

References

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2. Fig. 1. Myeloperoxidase in the human arterial wall: a, A single mononuclear cell expressing myeloperoxidase in the area of fibrous cap dissection of an unstable atherosclerotic plaque; b, Multiple mononuclear cells expressing myeloperoxidase in the area of severe cap destruction of an unstable plaque; c, Mononuclear cells with myeloperoxidase in the cytoplasm in the adventitia under an unstable atherosclerotic plaque; d, Absence of intra- and extracellular myeloperoxidase deposits in the cap of a stable atherosclerotic plaque. Immunohistochemical staining using polyclonal anti-myeloperoxidase antibodies. Reaction visualization using 3,3'-diaminobenzidine, additional methyl green nuclear staining, ×600.

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3. Fig. 2. Smooth muscle cells and collagen–elastin scaffolds in various atherosclerotic lesions: a, Single smooth muscle cells with signs of cytoplasmic destruction and fragmentation in the intima of an unstable plaque; b, Destruction of elastic and collagen fibers, as well as fibrous cap rupture of an unstable plaque; no decrease in the number of smooth muscle cells (c) or damage to the collagen–elastin scaffold (d) in the cap of a stable plaque. a, c, Immunohistochemical staining using monoclonal antibodies to human smooth muscle cells (×600); b, d, Detection of elastic and collagen fibers. Weigert Van Gieson staining; b, ×200, d, ×600.

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