Endothelium-Mimetic Surface Modification Improves Antithrombogenicity and Enhances Patency of Vascular Grafts in Rats and Pigs.

Endothelium-Mimetic Surface Modification Improves Antithrombogenicity and Enhances Patency of Vascular Grafts in Rats and Pigs.
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DOI:
10.1016/j.jacbts.2022.12.009
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发表时间:
2023-07
影响因子:
9.7
通讯作者:
Zhao, Qiang
Zhao, Qiang
中科院分区:
医学1区
文献类型:
--
作者:
Wei, Yongzhen;Jiang, Huan;Chai, Chao;Liu, Pei;Qian, Meng;Sun, Na;Gao, Man;Zu, Honglin;Yu, Yongquan;Ji, Guangbo;Zhang, Yating;Yang, Sen;He, Ju;Cheng, Jiansong;Tian, Jinwei;Zhao, Qiang

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TM和eNOS被确定为人类动脉粥样硬化颈动脉内皮抗血栓形成功能的关键因素。通过固定化重组TM和负责转化外源性NO前药的工程化半乳糖苷酶,对聚己内酯血管移植物进行内皮模拟表面修饰。TM和NO的表面修饰协同增强了大鼠和猪模型血管移植物的抗血栓性和通畅性。我们首先确定血栓调节蛋白(TM)和内皮型一氧化氮(NO)合酶作为人类动脉粥样硬化颈动脉内皮抗血栓形成功能的关键因素。然后,将重组TM和负责转化外源性NO前药的工程化半乳糖苷酶固定在血管移植物的表面上。TM和NO的表面修饰协同增强了血管移植物的抗血栓性和通畅性。重要的是,我们发现TM和NO的组合也促进内皮化,而它减少了不利的内膜增生,这是维持血管稳态的关键,如在大鼠和猪模型中所证实的。
TM and eNOS were identified as key factors for the antithrombogenic function of the endothelium in human atherosclerotic carotid arteries. Endothelium-mimetic surface modification of polycaprolactone vascular grafts was carried out via immobilization of recombinant TM and an engineered galactosidase responsible for the conversion of an exogenous NO prodrug. Surface modification by TM and NO cooperatively enhanced the antithrombogenicity and patency of vascular grafts in rat and pig models. We first identified thrombomodulin (TM) and endothelial nitric oxide (NO) synthase as key factors for the antithrombogenic function of the endothelium in human atherosclerotic carotid arteries. Then, recombinant TM and an engineered galactosidase responsible for the conversion of an exogenous NO prodrug were immobilized on the surface of the vascular grafts. Surface modification by TM and NO cooperatively enhanced the antithrombogenicity and patency of vascular grafts. Importantly, we found that the combination of TM and NO also promoted endothelialization, whereas it reduced adverse intimal hyperplasia, which is critical for the maintenance of vascular homeostasis, as confirmed in rat and pig models.
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