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Metalloproteases and intracranial vascular lesions
P Gaetani1, R Rodriguez y Baena, F Tartara
1Section of Neurosurgery, Istituto Clinico Humanitas, Milan, Italy.
Abstract:
Recent studies have suggested that metalloproteinases (MMP) might be involved in the pathogenesis of cerebral aneurysm formation and rupture and that elevated serum levels of MMP may effectively be considered as possible markers of cerebrovascular malformations. The present study was planned in order to verify if serum levels of MMPs may be the mirror of the MMP activity in the wall of intracranial aneurysms, reflecting the predisposition to aneurysm development and/or rupture. A series of 84 patients operated for intracranial cerebrovascular lesions (63 aneurysms and 21 arterovenous malformations (AVM)) and 20 controls entered the study. Among the 63 cases of intracranial aneurysms, nine were discovered before rupture, while 54 patients were included after subarachnoid hemorrhage (SAH). Using radioimmunoassay, plasma elastase levels were measured in all cases, while in 25 cases, when aneurysmectomy was possible, the activity of elastase and collagenase were measured in aneurysm samples. Mean plasma elastase level in patients bearing both an intracranial aneurysm or an intracranial AVM was significantly higher than in controls, while there was no significant difference between plasmatic level of elastase in patients with aneurysms when compared with patients bearing an intracranial AVM; there was no significant difference between mean elastase level in patients who suffered SAH and patients bearing an intracranial unruptured aneurysm. The activity of elastase and collagenase measured in the aneurysm wall were significantly higher in cases of ruptured than in unruptured aneurysms. The present results show that plasmatic level of elastase does not reflect the activity of MMP as measured in the aneurysm wall and that the patterns of MMP activities measured in the aneurysm wall differ considerably at different stages of SAH. This suggests that local rather than systemic changes in metalloproteases activity might be involved in cerebral aneurysm formation and rupture.
Insights
Systemic metalloproteinase (MMP) levels do not reflect local activity in cerebral aneurysms. MMP activity in aneurysm walls, not blood levels, correlates with rupture risk, suggesting localized processes in aneurysm pathogenesis.
Area of Science:
- Neuroscience
- Biochemistry
- Vascular Biology
Background:
- Metalloproteinases (MMP) are implicated in cerebral aneurysm formation and rupture.
- Elevated serum MMP levels are potential markers for cerebrovascular malformations.
Purpose of the Study:
- To determine if serum MMP levels mirror MMP activity within intracranial aneurysm walls.
- To investigate the relationship between MMP activity and aneurysm development/rupture predisposition.
Main Methods:
- Radioimmunoassay to measure plasma elastase levels in 84 patients (63 aneurysms, 21 AVMs) and 20 controls.
- Assay of elastase and collagenase activity in aneurysm wall samples from 25 patients.
- Comparison of MMP levels and activities between patient groups (aneurysm vs. AVM, ruptured vs. unruptured aneurysms) and controls.
Main Results:
- Plasma elastase levels were significantly higher in patients with intracranial aneurysms or AVMs compared to controls.
- No significant difference in plasma elastase between aneurysm and AVM patients, or between ruptured and unruptured aneurysm patients.
- Significantly higher elastase and collagenase activity in the walls of ruptured aneurysms versus unruptured ones.
Conclusions:
- Plasma elastase levels do not accurately reflect MMP activity within the aneurysm wall.
- MMP activity patterns in aneurysm walls vary with subarachnoid hemorrhage (SAH) stage.
- Local MMP activity, rather than systemic levels, is likely crucial in cerebral aneurysm formation and rupture.