Plasminogen is not required for neointima formation in a mouse model of vein graft stenosis.
Plasminogen is not required for neointima formation in a mouse model of vein graft stenosis.
复制标题
DOI：
10.1161/01.res.84.8.883
复制
发表时间：
1999-04
影响因子：
20.1
通讯作者：
C. Shi;A. Patel;D. Zhang;H. Wang;P. Carmeliet;G. Reed;M. -. Lee;E. Haber;N. Sibinga
中科院分区：
文献类型：
--
作者：
C. Shi;A. Patel;D. Zhang;H. Wang;P. Carmeliet;G. Reed;M. -. Lee;E. Haber;N. Sibinga
最近对缺乏纤溶酶原的小鼠的研究已经确定了这种酶原在动脉重塑中的关键作用。为了允许在静脉损伤的分析中使用这些（和其他）转基因小鼠，我们开发了一种模型，其中从小鼠的颈外静脉切下的贴片被移植以修复其颈动脉中的手术创建的缺损。在野生型小鼠中，静脉移植物显示出初始内皮剥脱和新生内膜形成，其以类似于人类静脉移植物疾病的方式进行性和可重复地扩张，尽管速度加快。新生内膜在第7天和第20天分别占血管腔的37+/-4.6%和66+/-5.7%。增殖细胞核抗原染色评估的新生内膜细胞增殖指数为50.6+/-3。第7天为6%，第20天为15.2 ± 2.0%。第7天时，CD 45阳性白细胞和α-肌动蛋白阳性平滑肌细胞分别占内膜面积的9.5+/-1.0%和9.9+/-1.1%，后者在第20天时增加至40.9+/-2.6%。第7天胶原蛋白占内膜面积的6.8 ± 0.7%，第20天为20.7 ± 1.8%。令人惊讶的是，即使在纤溶酶原-/-小鼠中由于静电和免疫介导的损伤导致的动脉新生内膜形成受损，在我们的研究中，这些小鼠中的静脉移植物新生内膜形成与对照组没有显著差异（70.9+/-6.4vs65.6 +/-4.4%管腔闭塞，P=NS）。因此，纤溶酶蛋白水解，虽然在动脉损伤后细胞外基质降解和细胞迁移中至关重要，但在静脉移植物新生内膜形成中似乎并不那么重要，这可能是因为正常静脉壁中细胞迁移的结构屏障相对缺乏。这种新的静脉移植物损伤模型将有助于进一步研究动脉和静脉组织对损伤反应的差异。
Recent studies of mice that lack plasminogen have identified a critical role for this zymogen in arterial remodeling. To permit the use of these (and other) genetically modified mice in the analysis of venous injury, we developed a model in which a patch cut from the external jugular vein of a mouse is grafted to repair a surgically created defect in its carotid artery. In wild-type mice, the venous graft showed initial endothelial denudation and formation of a neointima that progressively and reproducibly expanded in a manner analogous to human vein graft disease, albeit at an accelerated pace. This neointima occupied 37+/-4.6% of the vessel lumen at day 7 and 66+/-5.7% at day 20. The proliferative index of neointimal cells assessed by proliferating cell nuclear antigen staining was 50.6+/-3. 6% at day 7 and 15.2+/-2.0% at day 20. CD45-positive leukocytes and alpha-actin-positive smooth muscle cells accounted for 9.5+/-1.0% and 9.9+/-1.1% of intimal area at day 7, respectively, with the latter increasing to 40.9+/-2.6% at day 20. Collagen accounted for 6.8+/-0.7% of intimal area at day 7 and 20.7+/-1.8% at day 20. Surprisingly, even though arterial neointima formation due to electrostatic and immune-mediated injury is impaired in plasminogen -/- mice, in our study vein graft neointima formation in these mice was not significantly different from that in controls (70.9+/-6.4 versus 65.6+/-4.4% luminal occlusion, P=NS). Thus, plasmin proteolysis, although critical in extracellular matrix degradation and cellular migration after arterial injury, does not appear to be so important in vein graft neointima formation, perhaps because of the relative lack of structural barriers to cellular migration in the normal vein wall. This novel model of vein graft injury should be useful for further studies of differences in the response to injury of arterial and venous tissues.