材料科学
谷氨酰胺合成酶
生物医学工程
细胞
内皮干细胞
谷氨酰胺
细胞生物学
生物物理学
医学
生物化学
化学
生物
氨基酸
体外
作者
Xinbo Wei,Li Wang,Xing Zheng,Peng Chen,Xi He,Xiaoye Tuo,Haoran Su,Gang Zhou,Haifeng Liu,Yubo Fan
出处
期刊:Biomaterials
[Elsevier]
日期:2024-10-05
卷期号:314: 122877-122877
标识
DOI:10.1016/j.biomaterials.2024.122877
摘要
Endothelial cell (EC) dysfunction within the aorta has long been recognized as a prominent contributor to the progression of atherosclerosis and the subsequent failure of vascular graft transplantation. However, the direct relationship between EC dysfunction and vascular remodeling remains to be investigated. In this study, we sought to address this knowledge gap by employing a strategy involving the release of glutamine synthetase (GS), which effectively activated endothelial metabolism and mitigates EC dysfunction. To achieve this, we developed GS-loaded small-diameter vascular grafts (GSVG) through the electrospinning technique, utilizing dual-component solutions consisting of photo-crosslinkable hyaluronic acid and polycaprolactone. Through an in vitro model of oxidized low-density lipoprotein-induced injury in human umbilical vein endothelial cells (HUVECs), we provided compelling evidence that the GSVG promoted the restoration of motility, angiogenic sprouting, and proliferation in dysfunctional HUVECs by enhancing cellular metabolism. Furthermore, the sequencing results indicated that these effects were mediated by miR-122-5p-related signaling pathways. Remarkably, the GSVG also exhibited regulatory capabilities in shifting vascular smooth muscle cells towards a contractile phenotype, mitigating inflammatory responses and thereby preventing vascular calcification. Finally, our data demonstrated that GS incorporation significantly enhanced re-endothelialization of vascular grafts in a ferric chloride-injured rat model. Collectively, our results offer insights into the promotion of re-endothelialization in vascular grafts by restoring dysfunctional ECs through the augmentation of cellular metabolism.
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