Netrin-1 Promotes Inflammation Resolution to Achieve Endothelialization of Small-Diameter Tissue Engineering Blood Vessels by Improving Endothelial Progenitor Cells Function In Situ.
Netrin-1 Promotes Inflammation Resolution to Achieve Endothelialization of Small-Diameter Tissue Engineering Blood Vessels by Improving Endothelial Progenitor Cells Function In Situ.
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Netrin-1 通过改善原位内皮祖细胞功能促进炎症消退，实现小直径组织工程血管的内皮化
DOI：
10.1002/advs.201700278
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发表时间：
2017-12
期刊：
影响因子：
--
通讯作者：
Zhu C
中科院分区：
文献类型：
--
作者：
Li Y;Wan S;Liu G;Cai W;Huo D;Li G;Yang M;Wang Y;Guan G;Ding N;Liu F;Zeng W;Zhu C
在血管替代治疗中，小直径组织工程血管（小直径TEBVs） （< 6mm）的移植常常因为早期血栓形成和长期慢性炎症而失败。小直径tebv移植中涉及的特定炎症状态尚不清楚，促进炎症消退是否对小直径tebv治疗有用还需要研究。神经突起取向因子1 （Netrin - 1）存在于天然血管内皮细胞中，具有抗炎作用。这项工作通过使用一层一层的自组装来解决炎症，产生了网状蛋白1修饰的小直径tebv。结果表明，netrin - 1重编程巨噬细胞（MΦ），使其具有抗炎表型，并随着时间的推移促进MΦ从炎症部位的浸润和随后的外排，从而改善局部微环境和早期归巢内皮祖细胞（EPCs）的功能。经netrin - 1修饰的小直径tebv在30天后实现内皮化，并在14个月时保持通畅。这些发现表明，及时促进炎症的消退对于诱导小直径tebv内皮化、预防早期血栓形成和慢性炎症相关问题是必要的。此外，这项工作发现MΦ‐衍生的外泌体可以靶向和调节EPCs，这可能作为治疗其他炎症性疾病的有用方法。
The transplant of small‐diameter tissue engineering blood vessels (small‐diameter TEBVs) (<6 mm) in vascular replacement therapy often fails because of early onset thrombosis and long‐standing chronic inflammation. The specific inflammation state involved in small‐diameter TEBVs transplants remains unclear, and whether promoting inflammation resolution would be useful for small‐diameter TEBVs therapy need study. The neural protuberant orientation factor 1 (Netrin‐1) is found present in endothelial cells of natural blood vessels and has anti‐inflammatory effects. This work generates netrin‐1‐modified small‐diameter TEBVs by using layer‐by‐layer self‐assembly to resolve the inflammation. The results show that netrin‐1 reprograms macrophages (MΦ) to assume an anti‐inflammatory phenotype and promotes the infiltration and subsequent efflux of MΦ from inflamed sites over time, which improves the local microenvironment and the function of early homing endothelial progenitor cells (EPCs). Small‐diameter TEBVs modified by netrin‐1 achieve endothelialization after 30 d and retain patency at 14 months. These findings suggest that promoting the resolution of inflammation in time is necessary to induce endothelialization of small‐diameter TEBVs and prevent early thrombosis and problems associated with chronic inflammation. Furthermore, this work finds that the MΦ‐derived exosomes can target and regulate EPCs, which may serve as a useful treatment for other inflammatory diseases.
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影响因子：
7.7
作者：
Hasegawa T;Hall CJ;Crosier PS;Abe G;Kawakami K;Kudo A;Kawakami A
通讯作者：
Kawakami A
影响因子：
20.3
作者：
Paggetti, Jerome;Haderk, Franziska;Moussay, Etienne
通讯作者：
Moussay, Etienne
影响因子：
20.1
作者：
Krishnamurthy P;Thal M;Verma S;Hoxha E;Lambers E;Ramirez V;Qin G;Losordo D;Kishore R
通讯作者：
Kishore R
DOI：
10.1073/pnas.0511011103
发表时间：
2006-04-25
影响因子：
11.1
作者：
Nguyen, A;Cai, H
通讯作者：
Cai, H
影响因子：
17.1
作者：
Dahl, Shannon L. M.;Kypson, Alan P.;Niklason, Laura E.
通讯作者：
Niklason, Laura E.