Expression of alpha2-macroglobulin, neutrophil elastase, and interleukin-1alpha differs in early-stage and late-stage atherosclerotic lesions in the arteries of the circle of Willis.
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 alpha(2)-macroglobulin (A2M), the neutrophil elastase (NE)-an enzyme degrading elastin and collagen fibers-and the proinflammatory protein interleukin-1alpha (IL-1alpha) 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-1alpha. In initial AS lesions A2M was found, whereas NE and IL-1alpha were absent. NE and IL-1alpha 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-1alpha 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-1alpha 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-1alpha 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.
Larionov
Sergey
S
Department of Neuropathology, University of Bonn, Sigmund Freud Strasse 25, 53105, Bonn, Germany.
Dedeck
Oliver
O
Birkenmeier
Gerd
G
Thal
Dietmar Rudolf
DR
D000368:Aged; D000369:Aged, 80 and over; D001161:Arteriosclerosis / Q000145:classification / Q000378:metabolism* / Q000473:pathology; D002941:Circle of Willis / Q000378:metabolism*; D005260:Female; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism*; D019272:Leukocyte Elastase / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011180:Postmortem Changes; D013997:Time Factors; D000511:alpha-Macroglobulins / Q000378:metabolism*
D053582:Interleukin-1alpha; D000511:alpha-Macroglobulins; D019272:Leukocyte Elastase