Choke Edward, Thompson Matthew M, Dawson Joseph, Wilson W Richard W, Sayed Saiqa, Loftus Ian M, Cockerill Gillian W
Department of Cardiovascular Science, St George's, University of London, London SW17 0RE, UK.
Arterioscler Thromb Vasc Biol. 2006 Sep;26(9):2077-82. doi: 10.1161/01.ATV.0000234944.22509.f9. Epub 2006 Jun 29.
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.
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 alpha(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.
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.
基质金属蛋白酶（MMP）活性与腹主动脉瘤（AAA）破裂有关。中膜新生血管形成（MNV）是AAA的一种组织病理学特征，涉及MMP对细胞外基质的蛋白水解降解，以促进内皮细胞迁移。MNV在动脉瘤破裂中的作用尚不清楚。本研究调查了动脉瘤破裂时MNV是否增加。
对12例破裂性AAA的动脉瘤破裂边缘活检样本与来自破裂水平的动脉瘤壁及前囊的对照活检样本进行比较。另外从10例未破裂AAA的前囊中获取对照样本。免疫组化后，采用形态计量分析对MNV、微血管直径、成熟指数和炎性浸润进行定量。使用定量实时聚合酶链反应对促血管生成介质的表达进行定量。与前囊和破裂水平的动脉瘤壁相比，破裂边缘活检样本中的MNV增加（P<0.001），且由直径较小（P<0.001）和更不成熟的微血管组成（P<0.001）。破裂边缘活检样本中α(v)整合素、血管内皮生长因子、血管内皮钙黏蛋白、单核细胞趋化蛋白-1和波形蛋白的mRNA表达增加（P<0.05）。
本研究表明动脉瘤破裂边缘的中膜新生血管形成增加，促血管生成细胞因子过度表达。需要进一步研究这种血管生成反应是否是动脉瘤破裂的致病因素。
