Dissecting VEGF-induced acute versus chronic vascular hyperpermeability: Essential roles of dimethylarginine dimethylaminohydrolase-1.
Dissecting VEGF-induced acute versus chronic vascular hyperpermeability: Essential roles of dimethylarginine dimethylaminohydrolase-1.
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DOI：
10.1016/j.isci.2021.103189
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发表时间：
2021-10-22
期刊：
影响因子：
5.8
通讯作者：
Mukhopadhyay D
中科院分区：
文献类型：
--
作者：
Wang Y;Angom RS;Kulkarni TA;Hoeppner LH;Pal K;Wang E;Tam A;Valiunas RA;Dutta SK;Ji B;Jarzebska N;Chen Y;Rodionov RN;Mukhopadhyay D
血管内皮细胞生长因子(VEGF)是血管通透性的关键调节因子。在此，我们旨在了解急性和慢性暴露血管内皮生长因子是如何导致不同水平的血管通透性的。我们证明，与急性暴露相比，慢性暴露导致VEGFR2和c-Src的磷酸化水平降低，而一氧化氮(NO)水平稳步上升。利用热诱导的血管内皮生长因子转基因斑马鱼(Danio Rerio)，建立结合分割技术的定量算法，实时监测急性和慢性血管内皮细胞生长因子诱导的血管高通透性。重要的是，二甲基精氨酸二甲氨基水解酶-1(DDAH1)是一种产生NO的重要酶，在培养的人细胞、斑马鱼模型和Miles实验中都发挥着重要的作用。综上所述，我们的数据揭示了急性和慢性的血管内皮生长因子暴露诱导不同的信号通路，并确认DDAH1是血管高通透性介导的发病机制的关键参与者和潜在的治疗靶点。慢性暴露血管内皮生长因子诱导内皮细胞不同的信号模式一种新的算法可以精确地定量斑马鱼模型的血管通透性DDAH1作为血管内皮生长因子诱导的血管高通透性心血管药物的一种新的介体；分子遗传学
Vascular endothelial cell growth factor (VEGF) is a key regulator of vascular permeability. Herein we aim to understand how acute and chronic exposures of VEGF induce different levels of vascular permeability. We demonstrate that chronic VEGF exposure leads to decreased phosphorylation of VEGFR2 and c-Src as well as steady increases of nitric oxide (NO) as compared to that of acute exposure. Utilizing heat-inducible VEGF transgenic zebrafish (Danio rerio) and establishing an algorithm incorporating segmentation techniques for quantification, we monitored acute and chronic VEGF-induced vascular hyperpermeability in real time. Importantly, dimethylarginine dimethylaminohydrolase-1 (DDAH1), an enzyme essential for NO generation, was shown to play essential roles in both acute and chronic vascular permeability in cultured human cells, zebrafish model, and Miles assay. Taken together, our data reveal acute and chronic VEGF exposures induce divergent signaling pathways and identify DDAH1 as a critical player and potentially a therapeutic target of vascular hyperpermeability-mediated pathogenesis. Chronic VEGF exposure induces a different signaling pattern in endothelial cells A novel algorithm can precisely quantify the vascular permeability in zebrafish model DDAH1 acts as a novel mediator of VEGF-induced vascular hyperpermeability Cardiovascular medicine; Molecular genetics
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影响因子：
12.4
作者：
Chen H;Tong X;Lang L;Jacobson O;Yung BC;Yang X;Bai R;Kiesewetter DO;Ma Y;Wu H;Niu G;Chen X
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DOI：
10.1161/atvbaha.114.303215
发表时间：
2015-01
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
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DOI：
10.1073/pnas.041359198
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2001-02-27
影响因子：
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影响因子：
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作者：
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