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Published on: July 3, 2014
MMP-2/MMP-9 plasma level and brain expression in cerebral amyloid angiopathy-associated hemorrhagic stroke
Mar Hernandez-Guillamon1, Elena Martinez-Saez, Pilar Delgado
1Neurovascular Research Laboratory, Institut de Recerca Neurovascular Unit. Neurology and Medicine Departments, Universitat Autònoma de Barcelona, Spain. 31862jmv@comb.cat
Abstract:
Cerebral amyloid angiopathy (CAA) is one of the main causes of intracerebral hemorrhage (ICH) in the elderly. Matrix metalloproteinases (MMPs) have been implicated in blood-brain barrier disruption and ICH pathogenesis. In this study, we determined the levels MMP-2 and MMP-9 in plasma and their brain expression in CAA-associated hemorrhagic stroke. Although MMP-2 and MMP-9 plasma levels did not differ among patients and controls, their brain expression was increased in perihematoma areas of CAA-related hemorrhagic strokes compared with contralateral areas and nonhemorrhagic brains. In addition, MMP-2 reactivity was found in β-amyloid (Aβ)-damaged vessels located far from the acute ICH and in chronic microbleeds. MMP-2 expression was associated to endothelial cells, histiocytes and reactive astrocytes, whereas MMP-9 expression was restricted to inflammatory cells. In summary, MMP-2 expression within and around Aβ-compromised vessels might contribute to the vasculature fatal fate, triggering an eventual bleeding.
Insights
Matrix metalloproteinases (MMPs), specifically MMP-2, are elevated in the brain, not plasma, of elderly patients with cerebral amyloid angiopathy (CAA)-related hemorrhagic stroke, indicating a role in blood-brain barrier damage.
Area of Science:
- Neurology
- Pathology
- Vascular Biology
Background:
- Cerebral amyloid angiopathy (CAA) is a primary cause of intracerebral hemorrhage (ICH) in older adults.
- Matrix metalloproteinases (MMPs) are implicated in blood-brain barrier (BBB) disruption and ICH pathogenesis.
Purpose of the Study:
- To investigate the levels and brain expression of MMP-2 and MMP-9 in CAA-associated hemorrhagic stroke.
- To determine the cellular localization and potential role of MMPs in ICH associated with CAA.
Main Methods:
- Quantification of MMP-2 and MMP-9 plasma levels in patients with CAA-related ICH and controls.
- Analysis of MMP-2 and MMP-9 brain expression in perihematoma and contralateral areas of hemorrhagic brains, and in nonhemorrhagic brains.
- Immunohistochemical examination to identify the cellular sources of MMP expression.
Main Results:
- Plasma levels of MMP-2 and MMP-9 did not differ significantly between patients and controls.
- Brain expression of MMP-2 and MMP-9 was significantly increased in the perihematoma regions of CAA-related ICH compared to other brain areas.
- MMP-2 was found in β-amyloid (Aβ)-damaged vessels, including those distant from the acute ICH and in chronic microbleeds, associated with endothelial cells, histiocytes, and astrocytes.
- MMP-9 expression was primarily localized to inflammatory cells.
Conclusions:
- Elevated brain expression of MMP-2 around Aβ-compromised vessels may contribute to vascular damage and subsequent bleeding in CAA.
- MMP-2, rather than MMP-9, appears to play a more direct role in the vascular pathology of CAA-related ICH.
- Targeting MMP-2 activity could be a potential therapeutic strategy for preventing ICH in CAA patients.
