OBJECTIVE: alpha-Antitrypsin (AAT) and alpha(2)-macroglobulin (AMG) are elastase inhibitors that bind the enzyme and reduce measured levels of free elastase. It was recently demonstrated that some patients with intracranial aneurysms have significantly elevated plasma elastase (PE) levels. Although this elevation is unrelated to plasma AAT, it is unknown whether abnormal AAT phenotypes or reduced AMG levels pray a role. Moreover, the pathological significance of this elevation is not understood. METHODS: Plasma from 24 patients with aneurysms (ruptured, n = 15; unruptured, n = 9) and 10 age-matched patients who comprised a control group was analyzed for PE and AMG levels by enzyme-linked immunosorbent assay and for AAT phenotype by isoelectric focusing. Sections of superficial temporal artery obtained from these patients at the time of surgery were examined for evidence of elastin degradation by using a van Gieson stain, with scoring on a nine-point quantitative scale. RESULTS: Patients with aneurysms showed significantly elevated PE levels (119 +/- 28 versus 17 +/- 7 mu g/ml, P < 0.05), but AMG levels were not decreased. AAT phenotypic abnormalities were observed in 10% (2 of 20) of the patients with aneurysms, but this was not different from the expected population incidence (7%). Elastin degradation scores were significantly higher in patients with aneurysms than in patients in the control group (4.26 +/- 0.54 versus 1.21 +/- 0.43, P < 0.05). In addition, patients with higher elastase levels (>80 mu g/ml) demonstrated 55% higher degradation scores than did those with lower elastase levels (<80 mu g/ml). CONCLUSION: These data suggest that high PE levels may play a role in the systemic arterial elastin degradation seen in patients with intracranial aneurysms. These data also support the contention that elevated elastase levels are not the result of decreased protease inhibitor revels. Although PE levels were significantly higher for the entire group of patients with aneurysms, this assay has relatively low sensitivity for predicting the presence of unruptured aneurysms. Additional study is necessary to determine whether serum elastase levels greater than 80 mu g/ml, in the setting of other risk factors, are useful in identifying asymptomatic patients for additional screening.
