Shear stress and the endothelium
Shear stress and the endothelium
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DOI：
10.1046/j.1523-1755.1998.06720.x
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发表时间：
1998-09-01
影响因子：
19.6
通讯作者：
Liu, AL
中科院分区：
文献类型：
--
作者：
Ballermann, BJ;Dardik, A;Liu, AL
活体血管内皮细胞受到两种不同的血流动力学作用力的影响：一种是跨壁压力引起的血管壁扩张引起的周期性应变，另一种是切应力，即血流产生的摩擦力。剪切力作用于顶端细胞表面，使细胞沿血流方向变形，而壁扩张则使细胞向各个方向变形。剪应力响应至少部分不同于周期应变响应，这表明单靠细胞骨架应变不能解释这一现象。体外急性剪切力可引起内皮细胞迅速的细胞骨架重塑并激活信号通路，导致一氧化氮和前列环素的急性释放；转录因子核因子kappaB、c-fos、c-jun和SP-1的激活；以及ICAM-1、MCP-1、组织因子、血小板衍生生长因子-B(PDGF-B)、转化生长因子-β1：环氧合酶-II和内皮型一氧化氮合酶(ENOS)等基因的转录激活。因此，这种反应与EC对炎症细胞因子的反应有相似之处。相反，内皮细胞通过结构重塑和扁平化来适应慢性剪应力，以最大限度地减少剪应力。这样的细胞会非常贴附于它们的底物，并显示出分化的迹象。随着慢性剪切力的增加，粘附性增加已被利用来产生融合的EC单层血管移植物，并在体内植入后保留：从而克服了血管假体内皮化的主要障碍。
Vascular endothelial cells (ECs) in vivo are influenced by two distinct hemodynamic forces: cyclical strain due to vessel wall distention by transmural pressure, and shear stress, the frictional force generated by blood flow. Shear stress acts at the apical cell surface to deform cells in the direction of blood flow, wall distention tends to deform cells in all directions. The shear stress response differs, at least partly, from the cyclical strain response, suggesting that cytoskeletal strain alone cannot explain it. Acute shear stress in vitro elicits rapid cytoskeletal remodeling and activates signaling cascades in ECs, with the consequent acute release of nitric oxide and prostacyclin; activation of transcription factors nuclear factor (NF)kappa B, c-fos, c-jun and SP-1; and transcriptional activation of genes, including ICAM-1, MCP-1, tissue factor, platelet-derived growth factor-B (PDGF-B), transforming growth factor (TGF)-beta 1: cyclooxygenase-II, and endothelial nitric oxide synthase (eNOS). This response thus shares similarities with EC responses to inflammatory cytokines. In contrast, ECs adapt to chronic shear stress by structural remodeling and flattening to minimize shear stress. Such cells become very adherent to their substratum and show evidence of differentiation. Increased adhesion following chronic shear stress has been exploited to generate vascular grafts with confluent EC monolayers, retained after implantation in vivo: thus overcoming a major obstacle to endothelialization of vascular prostheses.