Decreased neointimal formation in Mac-1-/- mice reveals a role for inflammation in vascular repair after angioplasty
Decreased neointimal formation in Mac-1-/- mice reveals a role for inflammation in vascular repair after angioplasty
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DOI：
10.1172/jci7811
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发表时间：
2000-02-01
影响因子：
15.9
通讯作者：
Rogers, C
中科院分区：
文献类型：
--
作者：
Simon, DI;Chen, ZP;Rogers, C
炎症在动脉粥样硬化的发生和发展中起着至关重要的作用，但其在机械动脉损伤（即经皮腔内冠状动脉成形术，PTCA）后血管修复中的作用尚不清楚。在血管损伤的动物模型中，白细胞被募集作为内膜增厚的前兆。此外，白细胞活化的标志物-特别是β 2整合素Mac-1 （α M β 2，或CD11b/CD18）的表达增加，它负责白细胞与脱落血管上的血小板和纤维蛋白原的牢固粘附-预测PTCA后再狭窄。为了确定Mac-1介导的白细胞募集是否与新内膜形成有因果关系，我们对缺乏Mac-1的小鼠进行了一种新型的机械颈动脉扩张和完全内皮剥脱。我们现在报道，Mac-1的选择性缺失会损害经血小板的白细胞向血管壁的迁移，减少白细胞的积累。血管损伤后，内侧白细胞积聚减少，新内膜增厚明显减少。这些数据证实了炎症在新内膜增厚中的作用，并表明白细胞聚集到机械损伤的动脉可能阻止再狭窄。
Inflammation plays an essential role in the initiation and progression of atherosclerosis, but its role in vascular repair after mechanical arterial injury (i.e., percutaneous transluminal coronary angioplasty, PTCA) is unknown. In animal models of vascular injury, leukocytes are recruited as a precursor to intimal thickening. Furthermore, markers of leukocyte activation - in particular, increased expression of the beta 2-integrin Mac-1 (alpha M beta 2, or CD11b/CD18), which is responsible for firm leukocyte adhesion to platelets and fibrinogen on denuded vessels - predict restenosis after PTCA. To determine whether Mac-1-mediated leukocyte recruitment is causally related to neointimal formation, we subjected mice lacking Mac-1 to a novel form of mechanical carotid artery dilation and complete endothelial denudation. We now report that the selective absence of Mac-1 impairs transplatelet leukocyte migration into the vessel wall, reducing leukocyte accumulation over time. Diminished medial leukocyte accumulation was accompanied by markedly reduced neointimal thickening after vascular injury. These data establish a role for inflammation in neointimal thickening and suggest that leukocyte recruitment to mechanically injured arteries may prevent restenosis.