Effect of pulsatility on shear-induced extensional behavior of Von Willebrand factor.
Effect of pulsatility on shear-induced extensional behavior of Von Willebrand factor.
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脉动性对剪切诱导的von Willebrand因子延伸行为的影响。
DOI：
10.1111/aor.14133
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发表时间：
2022-05
影响因子：
2.4
通讯作者：
中科院分区：
文献类型：
--
作者：
植入连续流心室辅助装置（CF-VAD）的患者发生非手术出血的风险较高，推测与CF-VAD置入后脉动性丧失相关。据推测，连续剪切应力导致血管性血友病因子（vWF）的伸长和酶降解增加，vWF是血管损伤部位血栓形成的关键因素。然而，脉动性丧失对vWF解开行为的作用尚未得到广泛研究。将vWF分子固定在微流体装置的表面上，并使其经受各种脉动流分布，包括不同幅度的连续流和脉动流、脉动性的dQ/dt（即流速的一阶导数）和脉冲频率，以模拟有和没有CF-VAD支持的体内剪切流环境。使用全内反射荧光（TIRF）显微镜观察VWF延长。此外，从临床角度测量CF-VAD植入前后患者血液样本的vWF水平。据我们所知，这项工作是第一个提供直接，直观的观察单一vWF分子的延伸下控制脉动剪切流。与连续流相比，在脉动流下vWF（总样品大小n ~ 200个分子）的解散开显著减少（P < 0.01）。脉动幅度的增加进一步减少了解开长度，而较低的脉动频率（20与60脉冲/分钟）对最大或最小解开长度没有重大影响。对CF-VAD患者血液样本（n = 13）的评价表明，CF-VAD置入后vWF水平降低约40%（p < 0.01），从临床角度来看，这与单分子观察结果相关。与连续流相比，脉动流减少vWF的解折叠，并且20脉冲/分钟的较低脉冲频率产生与60脉冲/分钟相当的vWF解折叠。这些发现可能有助于了解CF-VAD置入后与搏动丧失相关的非手术出血，
Patients with continuous flow ventricular assist devices (CF-VADs) are at high risk for non-surgical bleeding, speculated to associate with the loss of pulsatility following CF-VAD placement. It has been hypothesized that continuous shear stress causes elongation and increased enzymatic degradation of von Willebrand Factor (vWF), a key player in thrombus formation at sites of vascular damage. However, the role of loss of pulsatility on the unravelling behavior of vWF has not been widely explored. vWF molecules were immobilized on the surface of microfluidic devices and subjected to various pulsatile flow profiles, including continuous flow and pulsatile flow of different magnitudes, dQ/dt (i.e. first derivative of flow rate) of pulsatility and pulse frequencies to mimic in vivo shear flow environments with and without CF-VAD support. VWF elongation was observed using total internal reflection fluorescence (TIRF) microscopy. Besides, vWF level is measured from patients’ blood sample before and after CF-VAD implantation from a clinical perspective. To our knowledge, this work is the first in providing direct, visual observation of single vWF molecule extension under controlled -pulsatile shear flow. Unravelling of vWF (total sample size n ~ 200 molecules) is significantly reduced under pulsatile flow (P < 0.01) compared to continuous flow. An increase in magnitude of pulsatility further reduces unravelling lengths, while lower frequency of pulsatility (20 vs. 60 pulses per min) does not have a major effect on the maximum or minimum unravelling lengths. Evaluation of CF-VAD patient blood samples (n = 13) demonstrates that vWF levels decreased by ~40% following CF-VAD placement (p < 0.01), which correlates to single-molecule observations from a clinical point of view. Pulsatile flow reduces unfolding of vWF compared to continuous flow and a lower pulse frequency of 20 pulses/minute yielded comparable vWF unfolding to 60 pulses/minute. These findings could shed light on non-surgical bleeding associated with the loss of pulsatility following CF-VAD placement,
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影响因子：
4.6
作者：
Bartoli, Carlo R.;Hennessy-Strahs, Samson;Smalling, Richard
通讯作者：
Smalling, Richard
影响因子：
4.2
作者：
Ising, Mickey S.;Sobieski, Michael A.;Giridharan, Guruprasad A.
通讯作者：
Giridharan, Guruprasad A.
DOI：
10.1073/pnas.0608422104
发表时间：
2007-05-08
影响因子：
11.1
作者：
Schneider, S. W.;Nuschele, S.;Schneider, M. F.
通讯作者：
Schneider, M. F.
影响因子：
3.4
作者：
Pirbodaghi, Tohid;Weber, Alberto;Vandenberghe, Stijn
通讯作者：
Vandenberghe, Stijn
影响因子：
4.8
作者：
Dong, JF;Moake, JL;Cruz, MA
通讯作者：
Cruz, MA