Blood flow-dependent arterial remodelling is facilitated by inflammation but directed by vascular tone

Blood flow-dependent arterial remodelling is facilitated by inflammation but directed by vascular tone
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DOI:
10.1093/cvr/cvn050
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发表时间:
2008-05-01
影响因子:
10.8
通讯作者:
VanBavel, Ed
VanBavel, Ed
中科院分区:
医学1区
文献类型:
--
作者:
Bakker, Erik N. T. P.;Matlung, Hanke L.;VanBavel, Ed

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目的改变血流影响血管张力,吸引炎症细胞,并导致微血管重塑。我们验证了炎症促进重塑反应的假说,但血管张力决定了重塑反应的方向(向内或向外)。方法和结果在体内结扎小鼠肠系膜阻力动脉以增加血流量或降低血流量。用活体显微镜观察血管张力的变化。在有或没有巨噬细胞耗尽的情况下,在2天后研究结构重塑。为了表征炎症反应,使用了免疫染色、共聚焦显微镜和实时荧光定量聚合酶链式反应(Real-time PCR)。为了说明血管张力在血管重塑中的作用,在器官培养过程中用血管扩张剂氨氯地平处理动脉。暴露在高血流量下的血管扩张,而低流量则导致收缩。1天后,炎性标志物在高流量和低流量时的表达增加很复杂,但非常相似。高流量血管和双流量血管外膜巨噬细胞数量均增加。巨噬细胞的耗尽消除了血流诱导的重塑。血管张力的操作逆转了向内重塑的反应,以响应两个血流。结论血流改变触发了炎症反应,从而促进重塑。血管张力是重塑反应方向的关键决定因素。
Aims Altered blood flow affects vascular tone, attracts inflammatory cells, and leads to microvascular remodelling. We tested the hypothesis that inflammation facilitates the remodelling response, but that vascular tone determines its direction (inward or outward).Methods and results Mouse mesenteric resistance arteries were ligated to create either increased blood flow or low blood flow in vivo. In vivo microscopy was used to determine changes in vascular tone. Structural remodelling was studied after 2 days, with or without macrophage depletion. In order to characterize the inflammatory response, immunostaining, confocal microscopy, and real-time PCR were used. To address the role of vascular tone in remodelling, arteries were treated with the vasodilator amlodipine during organ culture. Vessels exposed to high blood flow dilated, whereas low flow induced constriction. After 1 day, inflammatory markers showed a complex but remarkably similar increase in expression during high flow and low flow. Both high-flow and tow-flow vessels showed an increase in the number of adventitial macrophages. Depletion of macrophages eliminated flow-induced remodelling. Manipulation of vascular tone reversed inward remodelling in response to tow blood flow.Conclusion Altered blood flow triggers an inflammatory response that facilitates remodelling. Vascular tone is a crucial determinant of the direction of the remodelling response.