Vascular endothelial growth factor induces extracellular matrix proteins and osteopontin in the umbilical artery
Vascular endothelial growth factor induces extracellular matrix proteins and osteopontin in the umbilical artery
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DOI：
10.1016/j.avsg.2007.11.002
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发表时间：
2008-03-01
影响因子：
1.5
通讯作者：
Grimm, Daniela
中科院分区：
文献类型：
--
作者：
Infanger, Manfred;Grosse, Jirka;Grimm, Daniela
血管内皮生长因子（VEGF）是一种促有丝分裂、促血管生成和有效的血管通透性介质。它在损伤中起作用，在组织损伤的急性阶段导致水肿，并在恢复期间促进修复。我们最近发现，相当数量的血管受损的烧伤患者的VEGF血清水平显着增加。在这里，我们研究了VEGF对健康血管的影响，这些血管在重度烧伤患者中获得了相当的VEGF浓度。将VEGF 165（0.2mL的10 ng/ mL）或载体（盐水0.9%）在37 ℃下腔内应用于脐动脉90分钟。然后，将脐带灌注4小时，在灌注过程中，功能和生化参数保持在正常生理范围内。然后，应用形态计量学、天狼星红染色、偏光显微镜、蛋白质印迹分析和免疫组织化学对血管进行分析。此外，培养的人脐静脉内皮细胞（HUVECs）用VEGF或载体处理90分钟和5.5小时，以检查细胞外基质（ECM）蛋白和受体酪氨酸激酶。VEGF治疗的脐动脉显示出显着的组织水肿，同时增强层粘连蛋白和胶原蛋白1型，111型和IV型与对照动脉相比。我们检测到FIT-1、1710、骨桥蛋白和B-1-整联蛋白的增加。VEGF诱导层粘连蛋白在HUVECs早期通过流式细胞术测量。在平行，VEGF诱导了更高的量的骨桥蛋白，B-1-整合素，和这两种受体酪氨酸激酶在内皮细胞内90分钟。血管内皮生长因子的腔内应用增强ECM蛋白，骨桥蛋白，和B-1-整合素生产的内皮细胞，而它仍然产生组织水肿。即使靶血管未受损，VEGF也会在其产生水肿的早期启动血管重塑。VEGF诱导的骨桥蛋白和B 1-整合素在血管重构过程中可能起重要作用。
Vascular endothelial growth factor (VEGF) is a mitogenic, angiogenic, and potent mediator of vascular permeability. It plays a role in injuries, contributes to edema during the acute stage of tissue damage, and promotes repair during recovery. We recently showed that VEGF serum levels of burn patients with a considerable number of damaged vessels were significantly increased. Here, we study the effects of VEGF on healthy vessels treated with a comparable VEGF concentration achieved in patients suffering heavy burns. VEGF 165 (0.2 mL of 10 ng/ mL) or vehicle (saline 0.9%) was intraluminally applied to umbilical arteries for 90 min at 37 degrees C. Then, the cord was perfused for 4 hr. During perfusion, functional and biochemical parameters were kept within normal physiological ranges. Afterward, the vessels were analyzed applying morphometry, sirius red staining, polarization microscopy, Western blot analysis, and immunohistochemistry. Moreover, cultured human umbilical vein endothelial cells (HUVECs) were treated with VEGF or vehicle for 90 min and 5.5 hr to examine extracellular matrix (ECM) proteins and receptor tyrosine kinases. VEGF-treated umbilical arteries showed significant tissue edema and simultaneously an enhancement of laminin and collagen types 1, 111, and IV compared with control arteries. We detected an increase in FIt-1, 1710, osteopontin, and B-1-integrin. VEGF induced laminin early in HUVECs as measured by flow cytometry. In parallel, VEGF induced a higher amount of osteopontin, B-1-integrin, and both receptor tyrosine kinases in endothelial cells within 90 min. Intraluminal application of VEGF enhances ECM protein, osteopontin, and B-1-integrin production of the endothelium, while it still generates tissue edema. VEGF initiates vascular remodeling as early as it generates edema, even if the target vessel is not damaged. Osteopontin and B-1-integrin, both induced by VEGF, may play an important role in the vascular remodeling process.