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血管重塑由VEGFR3依赖性流体切应力设定点控制。

Vascular remodeling is governed by a VEGFR3-dependent fluid shear stress set point.

作者信息

Baeyens Nicolas, Nicoli Stefania, Coon Brian G, Ross Tyler D, Van den Dries Koen, Han Jinah, Lauridsen Holly M, Mejean Cecile O, Eichmann Anne, Thomas Jean-Leon, Humphrey Jay D, Schwartz Martin A

机构信息

Department of Internal Medicine, Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, United States.

Department of Biomedical Engineering, Yale University School of Engineering and Applied Science, New Haven, United States.

出版信息

Elife. 2015 Feb 2;4:e04645. doi: 10.7554/eLife.04645.

DOI:10.7554/eLife.04645
PMID:25643397
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4337723/
Abstract

Vascular remodeling under conditions of growth or exercise, or during recovery from arterial restriction or blockage is essential for health, but mechanisms are poorly understood. It has been proposed that endothelial cells have a preferred level of fluid shear stress, or 'set point', that determines remodeling. We show that human umbilical vein endothelial cells respond optimally within a range of fluid shear stress that approximate physiological shear. Lymphatic endothelial cells, which experience much lower flow in vivo, show similar effects but at lower value of shear stress. VEGFR3 levels, a component of a junctional mechanosensory complex, mediate these differences. Experiments in mice and zebrafish demonstrate that changing levels of VEGFR3/Flt4 modulates aortic lumen diameter consistent with flow-dependent remodeling. These data provide direct evidence for a fluid shear stress set point, identify a mechanism for varying the set point, and demonstrate its relevance to vessel remodeling in vivo.

摘要

在生长或运动条件下，或在从动脉狭窄或阻塞恢复过程中的血管重塑对健康至关重要，但其机制尚不清楚。有人提出，内皮细胞具有一个决定重塑的最佳流体剪切应力水平，即“设定点”。我们发现，人脐静脉内皮细胞在接近生理剪切力的流体剪切应力范围内反应最佳。在体内经历低得多血流的淋巴管内皮细胞也有类似效应，但在较低的剪切应力值时出现。VEGFR3水平是一种连接机械感觉复合体的组成部分，介导了这些差异。在小鼠和斑马鱼身上进行的实验表明，改变VEGFR3/Flt4水平可调节主动脉管腔直径，这与血流依赖性重塑一致。这些数据为流体剪切应力设定点提供了直接证据，确定了改变设定点的机制，并证明了其与体内血管重塑的相关性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c1/4337723/438980693de9/elife04645fs006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c1/4337723/5b5903014744/elife04645f001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c1/4337723/d859625727b2/elife04645f002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c1/4337723/e65d9f783763/elife04645fs001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c1/4337723/16fceea2a81f/elife04645f003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c1/4337723/0aceb2024ace/elife04645fs002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c1/4337723/097ad71e0597/elife04645f004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c1/4337723/91309c9449a5/elife04645fs003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c1/4337723/78ae16759adc/elife04645fs004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c1/4337723/16d1be7de6ca/elife04645f005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c1/4337723/9e5b00990e6a/elife04645f006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53c1/4337723/438980693de9/elife04645fs006.jpg

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