Systems Analysis of Thrombus Formation.
Systems Analysis of Thrombus Formation.
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DOI：
10.1161/circresaha.115.306824
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发表时间：
2016-04-29
影响因子：
20.1
通讯作者：
Diamond SL
中科院分区：
文献类型：
--
作者：
Diamond SL
血栓形成的系统分析旨在定量预测给定血管壁和血液动力学背景下的血液功能。与静脉和动脉血栓形成相关，血液系统生物学方法应提供凝块生长的速率和分子机制、血栓形成风险、药理学反应和新治疗靶点的效用的指标。作为具有聚合纤维蛋白基质的快速产生的多细胞聚集体，血凝块由在血液动力学条件下在空间和时间上传播的血小板内和周围的数百种独特反应产生。冠状动脉血栓形成主要由动脉粥样硬化斑块破裂、通过狭窄区域产生高壁剪切应力的复杂脉动流以及驱动凝血酶产生的斑块衍生的组织因子主导。相比之下，静脉血栓形成主要由停滞或抑制的血流、内皮炎症、白色血细胞衍生的组织因子和大量红细胞掺入。通过血管成像，使用计算流体动力学的患者特异性评估提供了局部血流动力学和血流储备分数的估计。血小板和凝血的高维离体表型现在可以在心脏病发作或中风的亚细胞到细胞到整个血管尺度上为多尺度计算机模拟提供动力。此外，综合系统生物学方法可以对各种药物干预或临床试验设计的安全性和有效性指标进行排名。
The systems analysis of thrombosis seeks to quantitatively predict blood function in a given vascular wall and hemodynamic context. Relevant to both venous and arterial thrombosis, a Blood Systems Biology approach should provide metrics for rate and molecular mechanisms of clot growth, thrombotic risk, pharmacological response, and utility of new therapeutic targets. As a rapidly created multicellular aggregate with a polymerized fibrin matrix, blood clots result from hundreds of unique reactions within and around platelets propagating in space and time under hemodynamic conditions. Coronary artery thrombosis is dominated by atherosclerotic plaque rupture, complex pulsatile flows through stenotic regions producing high wall shear stresses, and plaque-derived tissue factor driving thrombin production. In contrast, venous thrombosis is dominated by stasis or depressed flows, endothelial inflammation, white blood cell-derived tissue factor, and ample red blood cell incorporation. By imaging vessels, patient-specific assessment using computational fluid dynamics provides an estimate of local hemodynamics and fractional flow reserve. High dimensional ex vivo phenotyping of platelet and coagulation can now power multiscale computer simulations at the subcellular to cellular to whole vessel scale of heart attacks or strokes. Additionally, an integrated systems biology approach can rank safety and efficacy metrics of various pharmacological interventions or clinical trial designs.