Vascular extracellular matrix remodeling in cerebral aneurysms

Area of Science:

• Vascular biology
• Biochemistry
• Pathology

Background:

• Cerebral aneurysms are associated with changes in the extracellular matrix (ECM) and ECM-degrading proteases.
• Understanding the mechanisms of ECM remodeling is crucial for addressing aneurysm formation and rupture.

Purpose of the Study:

• To investigate the presence and extent of active extracellular matrix remodeling within human cerebral aneurysms.
• To identify specific proteases involved in ECM degradation in aneurysm tissue.

Main Methods:

• In situ zymography was used to detect gelatinolytic activity in aneurysm and control artery tissues.
• Immunohistochemical analysis identified the expression and localization of key proteases, including plasmin, tissue-type plasminogen activator (t-PA), urokinase-type plasminogen activator (u-PA), and matrix metalloproteinases (MMPs) such as MT1-MMP, MMP-2, and MMP-9.
• Aneurysm tissue from 23 patients was compared with 11 control basilar arteries.

Main Results:

• Focal gelatin lysis was significantly more prevalent in aneurysm tissue (17/21) compared to control arteries (2/11).
• Matrix metalloproteinases (MMPs) were the predominant enzyme family responsible for gelatin lysis, with significant contributions from serine proteinases.
• Increased expression of plasmin and MT1-MMP was observed in aneurysm tissue, while MMP-2 was also more common than in controls. MMP-9 and t-PA showed differential staining patterns between aneurysm and control tissues.

Conclusions:

• Cerebral aneurysm tissue exhibits heightened proteolytic activity, capable of degrading gelatin, and increased expression of plasmin, MT1-MMP, and MMP-2 compared to normal arteries.
• This elevated proteolytic activity likely contributes to the focal degradation of the vascular extracellular matrix.
• These findings suggest a significant role for ECM remodeling in the pathogenesis and progression of cerebral aneurysms.