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Vascular Biology |
From the Department of Cardiovascular Science, Academic Vascular Surgery Unit, St Georges, University of London, UK.
Correspondence to Gillian W. Cockerill, Senior Lecturer in Vascular Surgery, St Georges, University of London, Cranmer Terrace, London SW17 0RE, UK. E-mail gcockeri{at}sgul.ac.uk
Objective Matrix metalloproteinase (MMP) activity has been linked to abdominal aortic aneurysm (AAA) rupture. Medial neovascularization (MNV), a histopathologic characteristic of AAAs, involves proteolytic degradation of extracellular matrix by MMPs to facilitate endothelial cell migration. The role of MNV in aneurysm rupture is unknown. This study investigated whether MNV is increased in aneurysm rupture.
Methods and Results Biopsy samples from aneurysm rupture edge were compared with control biopsy samples from aneurysm wall at the level of rupture and from anterior sac in 12 ruptured AAAs. Further controls were obtained from anterior sac of 10 nonruptured AAAs. MNV, microvessel diameter, maturity index, and inflammatory infiltrate were quantified using morphometric analyses following immunohistochemistry. Expression of proangiogenic mediators was quantified using quantitative real-time-polymerase chain reaction. Compared with anterior sac and aneurysm wall at level of rupture, MNV was increased (P<0.001) in rupture edge biopsy samples and consisted of smaller diameter (P<0.001) and more immature microvessels (P<0.001). mRNA expression of
v-integrin, vascular endothelial growth factor, vascular endothelial-cadherin, monocyte chemoattractant protein-1, and vimentin was increased (P<0.05) in rupture edge biopsy samples.
Conclusions This study demonstrated increased medial neovascularization and overexpression of proangiogenic cytokines at aneurysm rupture edge. Further investigations into whether this angiogenic response was a causative factor of aneurysm rupture are needed.
This study investigated the extent of neovascularization in abdominal aortic aneurysm rupture and demonstrated increased medial neovascularization and overexpression of proangiogenic cytokines at aneurysm rupture edge. Further investigations into the role of angiogenesis in aneurysm rupture may open novel therapeutic avenues to prevent aneurysm rupture.
Key Words: aneurysm angiogenesis metalloproteinases neovascularization rupture
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