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Effects of physiologically relevant dynamic shear stress on platelet complement activation

机译:生理相关的动态切应力对血小板补体活化的影响

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Disturbed shear stress, commonly found in cardiovascular diseases, plays important roles in platelet activation and functions. It has been reported that when activated by elevated shear stress, platelets were able to support complement activation to completion. In this study, through a dynamic cone and plate shearing device, three physiologically relevant shear stresses were applied to platelets, mimicking the shear conditions when platelets pass through a normal left coronary artery (0.051Pa), a 60% stenosis (elevated shear stress at 6.5Pa for less than 0.1s), and when platelets are trapped in a recirculation zone past a stenosis (<0.5Pa). After shear exposure, platelet-surface complement activation (C1q, C4d, iC3b, and SC5b-9 depositions) was measured using a solid-phase ELISA approach and flow cytometry. Production of complement regulatory proteins C1-inhibitor (C1-INH) and complement receptor 1 (CR1), was also measured. Results demonstrated that low-pulsatile shear stress (recirculation) was able to initiate platelet complement activation, by increasing C1q deposition significantly. Both pathological shear stresses triggered significant increases in C1 inhibitor generation and noticeable changes in CR1 production, effectively preventing complement activation from completion. These results suggested that for platelets, low-pulsatile shear stress may be more pro-atherogenic, compared to elevated shear stress, especially when the shear stress exposure time is short.
机译:在心血管疾病中常见的扰动剪切应力在血小板活化和功能中起重要作用。据报道,当被升高的剪切应力激活时,血小板能够支持补体激活至完全。在这项研究中,通过动态锥板剪切装置,将三个与生理相关的剪切应力施加到血小板上,模拟了血小板通过正常的左冠状动脉(0.051Pa)时的剪切条件,狭窄率为60%( 6.5Pa(小于0.1s),并且当血小板被困在狭窄部位(<0.5Pa)的回流区中时。剪切暴露后,使用固相ELISA方法和流式细胞仪测量血小板表面补体激活(C1q,C4d,iC3b和SC5b-9沉积)。还测量了补体调节蛋白C1抑制剂(C1-INH)和补体受体1(CR1)的产生。结果表明,低搏动切应力(再循环)能够通过显着增加C1q沉积来启动血小板补体激活。两种病理切应力都触发了C1抑制剂生成的显着增加和CR1生成的显着变化,从而有效地阻止了补体激活的完成。这些结果表明,对于血小板而言,与升高的切应力相比,低脉动切应力可能更有利于动脉粥样硬化,尤其是当切应力暴露时间较短时。

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