Immaturity of microvessels in haemorrhagic plaques is associated with proteolytic degradation of angiogenic factors
Immaturity of microvessels in haemorrhagic plaques is associated with proteolytic degradation of angiogenic factors
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DOI：
10.1093/cvr/cvp253
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发表时间：
2010-01-01
影响因子：
10.8
通讯作者：
Houard, Xavier
中科院分区：
文献类型：
--
作者：
Le Dall, Julien;Ho-Tin-Noe, Benoit;Houard, Xavier
目的：我们调查的原因微血管不成熟和不稳定的人动脉粥样硬化lesions.Methods和结果人颈动脉粥样硬化斑块（n = 24）被归类为非出血性（NH）或出血性（Hem），根据其宏观方面和血红蛋白含量。通过免疫组化定量斑块微血管密度和成熟度。血管生成因子的表达通过免疫组织化学、原位杂交和ELISA进行研究。测试噬菌斑条件培养基的纤溶酶和弹性蛋白酶活性以及它们降解血管生成因子和诱导平滑肌细胞迁移的能力。与NH斑块相比，Hem斑块的微血管密度和白细胞浸润增加。斑块血管似乎脆弱的α-肌动蛋白阳性壁细胞的情况下，在大多数斑块血管。尽管Hem斑块中表达血管生成因子的微血管和白细胞数量增加，但在Hem斑块的条件培养基中发现血管内皮生长因子、胎盘生长因子和血管生成素-1水平较低。然而，NH和Hem斑块释放的血管不稳定因子血管生成素-2水平相似。此外，重组血管生成因子斑块提取物显示，所有的因素，但血管生成素-2选择性降解的纤溶酶和/或弹性蛋白酶释放的Hem斑块。此外，Hem斑块的条件培养基表现出降低诱导平滑肌细胞migration.Conclusion的能力，我们的研究结果提供的证据表明，斑块血管的不成熟与出血传送的白细胞和蛋白酶的血管生成因子的降解。
Aims We investigated the causes of microvessel immaturity and destabilization in human atherosclerotic lesions.Methods and results Human atherosclerotic carotid plaques (n = 24) were classified as non-haemorrhagic (NH) or haemorrhagic (Hem), according to their macroscopic aspect and haemoglobin content. Plaque microvessel density and maturity were quantified by immunohistochemistry. Expression of angiogenic factors was studied by immunohistochemistry, in situ hybridization, and ELISA. Plaque-conditioned media were tested for plasmin and elastase activities and for their ability to degrade angiogenic factors and to induce smooth muscle cell migration. Microvessel density and leucocyte infiltration were increased in Hem compared with NH plaques. Plaque vasculature appeared vulnerable as indicated by the absence of alpha-actin-positive mural cells in most plaque vessels. Despite increased numbers of angiogenic factor-expressing microvessels and leucocytes in Hem plaques, lower levels of vascular endothelial growth factor, placental growth factor, and angiopoietin-1 were found in conditioned media from Hem plaques. However, NH and Hem plaques released similar levels of the vascular destabilizing factor, angiopoietin-2. Addition of recombinant angiogenic factors to plaque extracts showed that all factors but angiopoietin-2 were selectively degraded by plasmin and/or elastase released from Hem plaques. Furthermore, conditioned media from Hem plaques showed a reduced ability to induce smooth muscle cell migration.Conclusion Our results provide evidence that immaturity of plaque vessels is associated with the degradation of angiogenic factors by haemorrhage-conveyed leucocytes and proteases.