Berceli Scott A, Jiang Zhihua, Klingman Nina V, Schultz Gregory S, Ozaki C Keith
Department of Surgery, University of Florida, Gainesville, Florida, USA.
J Surg Res. 2006 Aug;134(2):327-34. doi: 10.1016/j.jss.2005.12.030. Epub 2006 Feb 20.
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 (MMP)-2 and -9, key effectors of blood vessel architecture remodeling.
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.
Vein grafts demonstrated an early, transient increase in pro-MMP-9 within adherent monocytes and endothelial cells. This was followed by a delayed increase in smooth muscle cell active MMP-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.
These data provide evidence for unique and independent roles of MMP-2 and -9 in the process of hemodynamically driven vascular remodeling.
动脉和静脉移植物对血流减少的反应不同，动脉仅通过中膜有限的结构重组表现出内向重塑，而静脉移植物内膜增厚，外径变化不大。为了从机制上探索这种不同行为的生物学特性，我们假设血流介导的重塑中的这种差异反应是由基质金属蛋白酶（MMP）-2和-9的独特时间表达模式和功能活性驱动的，MMP-2和-9是血管结构重塑的关键效应因子。
在兔中，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7倍的血流差异。然后在1至14天的时间点采集静脉移植物和近端颈动脉进行形态学和生化研究。
静脉移植物在粘附的单核细胞和内皮细胞中显示出前MMP-9的早期短暂增加。随后平滑肌细胞活性MMP-2延迟增加，这与第7天和第14天内膜增厚的开始同时发生，并且在低血流时显著升高。相比之下，动脉中前MMP-9没有高于基线水平的升高，但在血流介导的血管直径变化之前显示出潜在MMP-2的短暂增加。
这些数据为MMP-2和-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。
