Understanding stenosis-induced platelet aggregation on a chip by high-speed optical imaging
Understanding stenosis-induced platelet aggregation on a chip by high-speed optical imaging
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通过高速光学成像了解芯片上狭窄引起的血小板聚集
DOI：
10.1016/j.snb.2021.131318
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Goda Keisuke
中科院分区：
文献类型：
--
作者：
Deng Yunjie;Duque Jaime Alvarez;Su Chengxun;Zhou Yuqi;Nishikawa Masako;Xiao Ting-Hui;Yatomi Yutaka;Hou Han Wei;Goda Keisuke
血管狭窄是动脉粥样硬化的病理标志，动脉粥样硬化是中风和心肌梗死等心血管疾病的主要原因。虽然已经通过体内和体外血管模型对狭窄诱导的血栓形成进行了广泛的研究，但由于缺乏高空间和时间分辨率的分析工具，血小板聚集的瞬时和动态过程仍不清楚。在这里，我们报告了使用体外微流体狭窄模型和光学时间拉伸成像系统对剪切诱导血小板聚集的时空分辨观察。具体来说，我们在三维狭窄模型中，在不同激动剂存在的情况下，每20分钟以单细胞分辨率表征血小板聚集物的大小、形状和数量。我们的研究结果表明，当狭窄和激动剂同时存在时，血小板聚集显著增强，从而提示动脉粥样硬化血流障碍和循环因子对血小板激活的协同作用。特别是，血小板被凝血酶受体激活肽6 （TRAP-6）激活，导致血小板聚集物分布广泛，聚集物明显大（面积约240µm2）。这些发现有望加深我们对狭窄诱导的血小板聚集机制的理解，并为开发更好的抗血栓治疗方法铺平道路。
Vascular stenosis is a pathological hallmark of atherosclerosis, the leading cause of cardiovascular diseases such as stroke and myocardial infarction. While stenosis-induced thrombus formation has been extensively studied using in vivo and in vitro vascular models, the transient and dynamic process of platelet aggregation remains unclear due to the lack of analytical tools with both high spatial and temporal resolution. Here we report spatiotemporally resolved observation of shear-induced platelet aggregation using an in vitro microfluidic stenosis model and an optical time-stretch imaging system. Specifically, we characterized the size, shape, and population of platelet aggregates at single-cell resolution every 20 min in the presence of different agonists in a 3D stenosis model. Our results indicate a significant enhancement in platelet aggregation when both stenosis and an agonist were present, thus suggesting a synergistic effect of atherogenic blood flow disturbance and circulating factors on platelet activation. In particular, platelets activated by thrombin receptor activator peptide 6 (TRAP-6) led to a broad-sized distribution of platelet aggregates with significantly large aggregates (>240 µm2in area). These findings are expected to deepen our understanding of the mechanism behind stenosis-induced platelet aggregation and pave the way for development of better antithrombotic therapeutics.
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影响因子：
9
作者：
N. Menon;Chengxun Su;K. Pang;Zhai Juan Phua;H. Tay;R. Dalan;Xiaomeng Wang;King Ho Holden Li;H. Hou
通讯作者：
N. Menon;Chengxun Su;K. Pang;Zhai Juan Phua;H. Tay;R. Dalan;Xiaomeng Wang;King Ho Holden Li;H. Hou
影响因子：
3.7
作者：
Dykes J;Lenshof A;Åstrand-Grundström IB;Laurell T;Scheding S
通讯作者：
Scheding S
速效 ADP 受体阻断在缺血性心脏病中的优势。
DOI：
--
发表时间：
2003
期刊：
Arteriosclerosis, Thrombosis and Vascular Biology
影响因子：
--
作者：
A. Nurden;P. Nurden
通讯作者：
P. Nurden
影响因子：
6.1
作者：
Menon, Nishanth Venugopal;Tay, Hui Min;Hou, Han Wei
通讯作者：
Hou, Han Wei
影响因子：
3.2
作者：
Herbig, Bradley A.;Yu, Xinren;Diamond, Scott L.
通讯作者：
Diamond, Scott L.