Laminar shear stress modulates endothelial luminal surface stiffness in a tissue-specific manner.
Laminar shear stress modulates endothelial luminal surface stiffness in a tissue-specific manner.
复制标题
层流剪切应力以组织特异性方式调节内皮腔表面刚度。
DOI：
10.1111/micc.12455
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Rabbany,SinaY
中科院分区：
文献类型：
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作者：
Merna,Nick;Wong,AndrewK;Barahona,Victor;Llanos,Pierre;Kunar,Balvir;Palikuqi,Brisa;Ginsberg,Michael;Rafii,Shahin;Rabbany,SinaY
内皮细胞在所有器官中形成血管床，并暴露于一系列调节细胞表型的机械力。我们试图确定内皮管腔表面硬度在微血管小鼠细胞中的层流剪切应力的组织特异性机械转导中的作用以及花生四烯酸在介导该反应中的作用。cm 2，在平行板流动室中持续12小时，使得能够对细胞进行真实的实时光学显微镜和原子力显微镜测量。结果肺内皮细胞平行于血流排列，而心脏内皮细胞没有。这种快速排列伴随着细胞刚度的增加。此外，花生四烯酸增加心脏内皮细胞的排列和刚度，以响应剪切应力。抑制肺内皮细胞和胚胎干细胞衍生的内皮细胞中的花生四烯酸可阻止细胞排列并降低细胞硬度。结论我们的研究结果表明，微血管细胞中内皮腔表面硬度的增加可能有助于响应层切应力的机械传导和排列。此外，花生四烯酸途径可能介导这种组织特异性过程。对这种反应的更好理解将有助于器官特异性血管疾病的治疗。
ObjectiveEndothelial cells form vascular beds in all organs and are exposed to a range of mechanical forces that regulate cellular phenotype. We sought to determine the role of endothelial luminal surface stiffness in tissue‐specific mechanotransduction of laminar shear stress in microvascular mouse cells and the role of arachidonic acid in mediating this response.MethodsMicrovascular mouse endothelial cells were subjected to laminar shear stress at 4 dynes/cm2for 12 hours in parallel plate flow chambers that enabled real‐time optical microscopy and atomic force microscopy measurements of cell stiffness.ResultsLung endothelial cells aligned parallel to flow, while cardiac endothelial cells did not. This rapid alignment was accompanied by increased cell stiffness. The addition of arachidonic acid to cardiac endothelial cells increased alignment and stiffness in response to shear stress. Inhibition of arachidonic acid in lung endothelial cells and embryonic stem cell‐derived endothelial cells prevented cellular alignment and decreased cell stiffness.ConclusionsOur findings suggest that increased endothelial luminal surface stiffness in microvascular cells may facilitate mechanotransduction and alignment in response to laminar shear stress. Furthermore, the arachidonic acid pathway may mediate this tissue‐specific process. An improved understanding of this response will aid in the treatment of organ‐specific vascular disease.