VEGF combined with DAPT promotes tissue regeneration and remodeling in vascular grafts.
VEGF combined with DAPT promotes tissue regeneration and remodeling in vascular grafts.
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DOI：
10.1093/rb/rbad088
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发表时间：
2023
影响因子：
6.7
通讯作者：
Duan, Chuanzhi
中科院分区：
文献类型：
--
作者：
Yang, Tao;Li, Guangxu;Li, Xifeng;Wei, Boyang;Su, Hengxian;Liu, Wenchao;Guo, Shenquan;Yang, Nan;Xu, Tao;Duan, Chuanzhi
以往对组织工程血管（TEBV）的研究主要集中于单侧的内膜或外膜，忽视了两层的同等重要性。同时，仅用血管内皮生长因子（VEGF）修饰的移植物的功效受到限制。在这里，我们开发了一种小直径移植物，可以逐渐释放 VEGF 和 γ 分泌酶抑制剂 IX (DAPT)，以增强内膜和外膜的组织再生和重塑。体外实验表明，VEGF和DAPT联合使用对内皮细胞具有优异的促增殖和促迁移作用。在体内，移植物中 VEGF 和 DAPT 的持续释放导致再生和重塑的改善。具体来说，在内膜中，平滑肌细胞更快的内皮化和再生导致更高的通畅率和更好的重塑。在外膜中，较高密度的新血管形成、M2巨噬细胞和成纤维细胞促进细胞向内生长和用自体新组织替换植入物。此外，蛋白质印迹分析证实再生的ECs具有功能，并且DAPT的作用与血管内皮生长因子受体2的表达增加有关。我们的研究表明，移植物中持续释放的VEGF和DAPT可以有效促进内膜和外膜的组织再生和重塑。这一进展有可能显着加速小直径 TEBV 的临床应用。
Previous research on tissue-engineered blood vessels (TEBVs) has mainly focused on the intima or adventitia unilaterally, neglecting the equal importance of both layers. Meanwhile, the efficacy of grafts modified with vascular endothelial growth factor (VEGF) merely has been limited. Here, we developed a small-diameter graft that can gradually release VEGF and γ secretase inhibitor IX (DAPT) to enhance tissue regeneration and remodeling in both the intima and adventitia. In vitro, experiments revealed that the combination of VEGF and DAPT had superior pro-proliferation and pro-migration effects on endothelial cells. In vivo, the sustained release of VEGF and DAPT from the grafts resulted in improved regeneration and remodeling. Specifically, in the intima, faster endothelialization and regeneration of smooth muscle cells led to higher patency rates and better remodeling. In the adventitia, a higher density of neovascularization, M2 macrophages and fibroblasts promoted cellular ingrowth and replacement of the implant with autologous neo-tissue. Furthermore, western blot analysis confirmed that the regenerated ECs were functional and the effect of DAPT was associated with increased expression of vascular endothelial growth factor receptor 2. Our study demonstrated that the sustained release of VEGF and DAPT from the graft can effectively promote tissue regeneration and remodeling in both the intima and adventitia. This development has the potential to significantly accelerate the clinical application of small-diameter TEBVs.
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影响因子：
64.8
作者：
Guarani V;Deflorian G;Franco CA;Krüger M;Phng LK;Bentley K;Toussaint L;Dequiedt F;Mostoslavsky R;Schmidt MHH;Zimmermann B;Brandes RP;Mione M;Westphal CH;Braun T;Zeiher AM;Gerhardt H;Dimmeler S;Potente M
通讯作者：
Potente M
影响因子：
14
作者：
Coronel MM;Geusz R;Stabler CL
通讯作者：
Stabler CL
器官特异性血管的基因靶向
影响因子：
20.1
作者：
Pu W;He L;Han X;Tian X;Li Y;Zhang H;Liu Q;Huang X;Zhang L;Wang QD;Yu Z;Yang X;Smart N;Zhou B
通讯作者：
Zhou B
影响因子：
14
作者：
Brewster, Luke P.;Bufallino, Dominick;Greisler, Howard P.
通讯作者：
Greisler, Howard P.
影响因子：
7.3
作者：
Fan, Linlin;Liu, Hao;Pang, Jinjiang
通讯作者：
Pang, Jinjiang