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Expression of α2-macroglobulin, neutrophil elastase, and interleukin-1α differs in early-stage and late-stage atherosclerotic lesions in the arteries of the circle of Willis

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Abstract

Different types of atherosclerotic (AS) lesions can be distinguished histologically and represent different stages of AS plaque development. Late-stage lesions more frequently develop complications such as plaque rupture and thrombosis with vessel occlusion than early AS lesions. To clarify whether protective, destructive, and inflammatory proteins are differentially expressed in early-stage and late-stage AS plaques we examined the proteinase inhibitor α2-macroglobulin (A2M), the neutrophil elastase (NE)—an enzyme degrading elastin and collagen fibers—and the proinflammatory protein interleukin-1α (IL-1α) in all types of AS plaques in the arteries of the circle of Willis from 78 human autopsy cases of both genders (61–91 years of age). Paraffin sections of AS plaques were immunostained with antibodies directed against A2M, NE and IL-1α. In initial AS lesions A2M was found, whereas NE and IL-1α were absent. NE and IL-1α became detectable as soon as a significant number of macrophages occurred within AS lesions. With increasing histopathological type of AS lesions, a marked increase of the area of the plaque exhibiting NE and IL-1α was observed. The area which exhibits A2M in AS plaques, on the other hand, did not vary significantly between the different stages. Thus, our results indicate a disproportionately high increase of the destructive enzyme NE and the proinflammatory protein IL-1α in relation to A2M with the progression of the grade of AS lesions pointing to the transgression of the protective capacity of A2M by NE and IL-1α in late-stage plaques. Therefore, our findings support the hypothesis that NE-induced tissue damage in late-stage AS plaques contributes to the development of plaque rupture and subsequent thrombosis.

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Acknowledgment

We thank Mrs. A. Hryschyk, Mrs. B. Vilz and Mr. H-U. Klatt for technical assistance.

This work was supported by BONFOR-grants O-154.0041 and O-154.0062 (D.R.T.).

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Authors and Affiliations

  1. Department of Neuropathology, University of Bonn, Sigmund Freud Strasse 25, 53105, Bonn, Germany

    Sergey Larionov, Oliver Dedeck & Dietmar Rudolf Thal

  2. Department of Biochemistry, University of Leipzig, 04103, Leipzig, Germany

    Gerd Birkenmeier

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  1. Sergey Larionov
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  2. Oliver Dedeck
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  4. Dietmar Rudolf Thal
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Correspondence to Dietmar Rudolf Thal.

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Larionov, S., Dedeck, O., Birkenmeier, G. et al. Expression of α2-macroglobulin, neutrophil elastase, and interleukin-1α differs in early-stage and late-stage atherosclerotic lesions in the arteries of the circle of Willis. Acta Neuropathol 113, 33–43 (2007). https://doi.org/10.1007/s00401-006-0134-0

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  • DOI: https://doi.org/10.1007/s00401-006-0134-0

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