Early differential MMP-2 and-9 dynamics during flow-induced arterial and vein graft adaptations
Early differential MMP-2 and-9 dynamics during flow-induced arterial and vein graft adaptations
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DOI：
10.1016/j.jss.2005.12.030
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发表时间：
2006-08-01
影响因子：
2.2
通讯作者：
Ozaki, C. Keith
中科院分区：
文献类型：
--
作者：
Berceli, Scott A.;Jiang, Zhihua;Ozaki, C. Keith
背景动脉和静脉移植物对流量减少的反应不同，动脉仅通过中膜的有限结构重组表现出向内重塑，静脉移植物形成增厚的内膜，外径变化不大。为了从机制上探索这种对比行为的生物学，我们假设这种血流介导的重塑中的差异反应是由基质金属蛋白酶（NMP）-2和-9（血管结构重塑的关键效应物）的独特时间表达模式和功能活性驱动的。在家兔中，双侧颈动脉静脉移植与单侧部分远端结扎相结合，以在两侧之间产生七倍的流量差。然后在1至14天的时间点收获静脉移植物和近端颈动脉进行形态学和生化研究。静脉移植物表现出粘附单核细胞和内皮细胞内的pro-AMP-9的早期短暂增加。随后是平滑肌细胞活性NMP-2的延迟增加，这与第7天和第14天内膜增厚的发生一致，并因低流量而显著升高。与此相反，动脉显示MMP-9原水平没有升高，但在血流介导的血管直径变化之前，表现出潜伏性MMP-2的短暂增加。这些数据为MMP-2和MMP-9在血流动力学驱动的血管重塑过程中的独特和独立作用提供了证据。(c)2006年爱思唯尔公司All rights reserved.
Background. Arteries and vein grafts respond differently to reductions in flow, with arteries demonstrating inward remodeling through only limited structural reorganization of the media and vein grafts developing a thickened intima, with little change in the external diameter. In an effort to mechanistically explore the biology of this contrasting behavior, we hypothesized that this differential response in flow-mediated remodeling is driven by unique temporal expression patterns and functional activities of the matrix metalloproteinase (NMP)-2 and -9, key effectors of blood vessel architecture remodeling.Material and methods. In rabbits, bilateral carotid vein grafting was coupled with unilateral partial distal ligation to create a sevenfold flow differential between sides. Vein grafts and proximal carotid arteries were then harvested for morphological and biochemical studies at time points ranging from 1 to 14 days.Results. Vein grafts demonstrated an early, transient increase in pro-AMP-9 within adherent monocytes and endothelial cells. This was followed by a delayed increase in smooth muscle cell active NMP-2, which was coincident with the onset of intimal thickening at days 7 and 14 and significantly elevated by low flow. In contrast, arteries showed no elevation in pro MMP-9 above baseline, but demonstrated a transient increase in latent MMP-2 preceding the flow-mediated change in vessel diameter.Conclusions. These data provide evidence for unique and independent roles of MMP-2 and -9 in the process of hemodynamically driven vascular remodeling. (c) 2006 Elsevier Inc. All rights reserved.