Expression of fibrinolytic genes in atherosclerotic abdominal aortic aneurysm wall. A possible mechanism for aneurysm expansion.
Expression of fibrinolytic genes in atherosclerotic abdominal aortic aneurysm wall. A possible mechanism for aneurysm expansion.
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动脉粥样硬化腹主动脉瘤壁中纤溶基因的表达。
DOI：
10.1172/jci118079
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Loskutoff,DJ
中科院分区：
文献类型：
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作者：
Schneiderman,J;Bordin,GM;Engelberg,I;Adar,R;Seiffert,D;Thinnes,T;Bernstein,EF;Dilley,RB;Loskutoff,DJ
动脉粥样硬化性腹主动脉瘤（AAA）的扩张归因于细胞外基质通过活性蛋白水解的重塑。我们用原位杂交技术分析了8例AAA患者动脉瘤壁纤溶基因的表达。所有标本均显示特定区域的炎性浸润，巨噬细胞样细胞表达尿激酶型纤溶酶原激活物（u-PA）和组织型PA（t-PA）mRNA。1型PA抑制剂（派-1）mRNA表达在所有标本的坏死性粥样硬化的基础上，也在一些炎性浸润，它经常共定位在含有u-PA和t-PA mRNA表达细胞的区域。然而，在这些领域，t-PA和u-PA的转录本的细胞分布远远超出了派-1的表达领域。这些观察结果表明，局部正在进行的蛋白水解过程中，这是只有部分抵消了更有限的派-1 mRNA的表达。大量毛细血管在所有炎性浸润中也很明显，可能反映了局部血管生成对活性细胞周围纤维蛋白溶解的反应。AAA壁中纤维蛋白溶解能力的增加可能促进血管生成，并有助于主动脉壁的局部蛋白水解降解，导致动脉瘤的物理弱化和主动扩张。
Expansion of atherosclerotic abdominal aortic aneurysm (AAA) has been attributed to remodeling of the extracellular matrix by active proteolysis. We used in situ hybridization to analyze the expression of fibrinolytic genes in aneurysm wall from eight AAA patients. All specimens exhibited specific areas of inflammatory infiltrates with macrophage-like cells expressing urokinase-type plasminogen activator (u-PA) and tissue-type PA (t-PA) mRNA. Type 1 PA inhibitor (PAI-1) mRNA was expressed at the base of the necrotic atheroma of all specimens and also within some of the inflammatory infiltrates where it frequently colocalized in regions containing u-PA and t-PA mRNA expressing cells. However, in these areas, the cellular distribution of the transcripts for t-PA and u-PA extended far beyond the areas of PAI-1 expression. These observations suggest a local ongoing proteolytic process, one which is only partially counteracted by the more restricted expression of PAI-1 mRNA. An abundance of capillaries was also obvious in all inflammatory infiltrates and may reflect local angiogenesis in response to active pericellular fibrinolysis. The increased fibrinolytic capacity in AAA wall may promote angiogenesis and contribute to local proteolytic degradation of the aortic wall leading to physical weakening and active expansion of the aneurysm.Images