PDF(Pubmed)
Abstract：
Acute cardiovascular events result from clots caused by the rupture and erosion of atherosclerotic plaques. This paper aimed to produce a functional biomimetic hydrogel of the neointimal layer of the atherosclerotic plaque that can support thrombogenesis upon exposure to human blood. A biomimetic hydrogel of the neointima was produced by culturing THP-1-derived foam cells within 3D collagen hydrogels in the presence or absence of atorvastatin. Prothrombin time and platelet aggregation onset were measured after exposure of the neointimal models to platelet-poor plasma and washed platelet suspensions prepared from blood of healthy, medication-free volunteers. Activity of the extrinsic coagulation pathway was measured using the fluorogenic substrate SN-17. Foam cell formation was observed following preincubation of the neointimal biomimetic hydrogels with oxidized LDL, and this was inhibited by pretreatment with atorvastatin. The neointimal biomimetic hydrogel was able to trigger platelet aggregation and blood coagulation upon exposure to human blood products. Atorvastatin pretreatment of the neointimal biomimetic layer significantly reduced its pro-aggregatory and pro-coagulant properties. In the future, this 3D neointimal biomimetic hydrogel can be incorporated as an additional layer within our current thrombus-on-a-chip model to permit the study of atherosclerosis development and the screening of anti-thrombotic drugs as an alternative to current animal models.
摘要：
急性心血管事件是由动脉粥样硬化斑块破裂和侵蚀引起的凝块引起的。本文旨在生产动脉粥样硬化斑块新内膜层的功能性仿生水凝胶，该水凝胶可以在暴露于人体血液后支持血栓形成。通过在存在或不存在阿托伐他汀的情况下在3D胶原水凝胶中培养THP-1衍生的泡沫细胞来产生新内膜的仿生水凝胶。在新内膜模型暴露于缺乏血小板的血浆和从健康血液中制备的洗涤的血小板悬浮液后，测量凝血酶原时间和血小板聚集开始。无药物志愿者使用荧光底物SN-17测量外源性凝血途径的活性。在新内膜仿生水凝胶与氧化LDL预孵育后观察到泡沫细胞形成，这被阿托伐他汀预处理抑制。新内膜仿生水凝胶在暴露于人类血液制品时能够触发血小板聚集和血液凝固。新内膜仿生层的阿托伐他汀预处理显着降低了其促聚集和促凝血特性。在未来,这种3D新生内膜仿生水凝胶可以作为额外的一层纳入我们目前的芯片血栓模型中,以允许研究动脉粥样硬化的发展和筛选抗血栓药物,作为目前动物模型的替代方案.
