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

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 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.

Association of the Glutathione S-transferase Omega-1 Ala140Asp Polymorphism With Cerebrovascular Atherosclerosis and Plaque-Associated Interleukin-1α Expression

“…Anti-␣ 2 -macroglobulin/AS plaque and neutrophil elastase/AS plaque did not differ among the GSTO1 genotypes, although neutrophil elastase/AS plaque was shown recently 6 to be associated with the expansion and type of AS ( Figure 1F-G).…”

“…Paraffin sections stained with anti-interleukin (IL)-1␣, anti-neutrophil elastase, and anti-␣ 2 -macroglobulin were quantitatively analyzed as described previously to determine the percentage of the AS plaque area stained with a given antibody. 6 Positive, negative, and blank controls were performed.…”

Common coding variant in SERPINA1 increases the risk for large artery stroke

“…The target enzyme of AAT, NE, is expressed by macrophages in human atherosclerotic plaques (17), particularly within advanced atherosclerotic lesions (31). AAT might facilitate protection against matrix breakdown by NE and clearance of lipoprotein deposits.…”

High Neutrophil Numbers in Human Carotid Atherosclerotic Plaques Are Associated With Characteristics of Rupture-Prone Lesions

“…1,2 Histological analysis of plaques from cerebral arteries has shown that the expression of neutrophil elastase is increased in late-stage plaques. 3 Epidemiological studies have shown that neutrophil counts in peripheral blood positively correlate with coronary atherosclerotic risk 4 and acute myocardial infarction risk. 5 Mouse studies reveal the accumulation of neutrophils in the luminal plaque region and adventitia of aortic plaques of mice that lack apolipoprotein E 6 and in lesions of low-density lipoprotein receptor-deficient mice.…”