Baek Kyung In, Chang Shyr-Shea, Chang Chih-Chiang, Roustaei Mehrdad, Ding Yichen, Wang Yixuan, Chen Justin, O'Donnell Ryan, Chen Hong, Ashby Julianne W, Xu Xiaolei, Mack Julia J, Cavallero Susana, Roper Marcus, Hsiai Tzung K
Department of Medicine and Bioengineering, University of California, Los Angeles, Los Angeles, CA, United States.
Department of Mathematics, University of California, Los Angeles, Los Angeles, CA, United States.
Front Cardiovasc Med. 2022 Mar 18;9:841101. doi: 10.3389/fcvm.2022.841101. eCollection 2022.
Mechano-responsive signaling pathways enable blood vessels within a connected network to structurally adapt to partition of blood flow between organ systems. Wall shear stress (WSS) modulates endothelial cell proliferation and arteriovenous specification. Here, we study vascular regeneration in a zebrafish model by using tail amputation to disrupt the embryonic circulatory loop (ECL) at 3 days post fertilization (dpf). We observed a local increase in blood flow and peak WSS in the Segmental Artery (SeA) immediately adjacent to the amputation site. By manipulating blood flow and WSS via changes in blood viscosity and myocardial contractility, we show that the angiogenic Notch-ephrinb2 cascade is hemodynamically activated in the SeA to guide arteriogenesis and network reconnection. Taken together, ECL amputation induces changes in microvascular topology to partition blood flow and increase WSS-mediated Notch-ephrinb2 pathway, promoting new vascular arterial loop formation and restoring microcirculation.
机械响应信号通路使相连网络中的血管能够在结构上适应器官系统间血流的分配。壁面剪应力(WSS)调节内皮细胞增殖和动静脉分化。在此,我们通过在受精后3天(dpf)进行尾部截肢来破坏斑马鱼胚胎循环环(ECL),从而在斑马鱼模型中研究血管再生。我们观察到截肢部位紧邻的节段动脉(SeA)中血流局部增加且WSS峰值出现。通过改变血液粘度和心肌收缩力来操纵血流和WSS,我们发现SeA中的血管生成Notch-ephrinb2级联反应在血流动力学上被激活,以引导动脉生成和网络重新连接。综合来看,ECL截肢会引起微血管拓扑结构变化,以分配血流并增强WSS介导的Notch-ephrinb2通路,促进新的血管动脉环形成并恢复微循环。