Akbari Ehsan, Spychalski Griffin B, Menyhert Miles M, Rangharajan Kaushik K, Tinapple Joseph W, Prakash Shaurya, Song Jonathan W
Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH, United States, 43210.
Department of Biomedical Engineering The Ohio State University, Columbus, OH, United States, 43210.
Biomater Biosyst. 2021 Sep;3. doi: 10.1016/j.bbiosy.2021.100020. Epub 2021 May 31.
Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid mediator of endothelial barrier function. Prior studies have implicated mechanical stimulation due to intravascular laminar shear stress in co-regulating S1P signaling in endothelial cells (ECs). Yet, vascular networks in vivo consist of vessel bifurcations, and this geometry generates hemodynamic forces at the bifurcation point distinct from laminar shear stress. However, the role of these forces at vessel bifurcations in regulating S1P-dependent endothelial barrier function is not known. In this study, we implemented a microfluidic platform that recapitulates the flow dynamics of vessel bifurcations with in situ quantification of the permeability of microvessel analogues. Co-application of S1P with impinging bifurcated fluid flow, which is characterized by approximately zero shear stress and 38 dyn•cm stagnation pressure at the vessel bifurcation point, promotes vessel stabilization. Similarly, co-treatment of S1P with 3 dyn•cm laminar shear stress is also protective of endothelial barrier function. Moreover, it is shown that vessel stabilization due to bifurcated fluid flow and laminar shear stress is dependent on S1P receptor 1 or 2 signaling. Collectively, these findings demonstrate the endothelium-protective function of fluid forces at vessel bifurcations and their involvement in coordinating S1P-dependent regulation of vessel permeability.
鞘氨醇-1-磷酸（S1P）是内皮屏障功能的一种生物活性鞘脂介质。先前的研究表明，血管内层流剪切应力引起的机械刺激共同调节内皮细胞（ECs）中的S1P信号传导。然而，体内的血管网络由血管分支组成，这种几何结构在分支点产生与层流剪切应力不同的血流动力学力。然而，这些力在血管分支处调节S1P依赖性内皮屏障功能中的作用尚不清楚。在本研究中，我们构建了一个微流控平台，该平台再现了血管分支的流动动力学，并对微血管类似物的通透性进行原位定量。将S1P与冲击性分支流体流共同应用，其特征是在血管分支点处剪切应力近似为零且停滞压力为38 dyn•cm，可促进血管稳定。同样，将S1P与3 dyn•cm的层流剪切应力共同处理也能保护内皮屏障功能。此外，研究表明，分支流体流和层流剪切应力引起的血管稳定依赖于S1P受体1或2信号传导。总的来说，这些发现证明了血管分支处流体力的内皮保护功能及其参与协调S1P依赖性血管通透性调节。
