Gan L, Miocic M, Doroudi R, Selin-Sjögren L, Jern S
Clinical Experimental Research Laboratory, Sahlgrenska University Hospital/Ostra, Göteborg, Sweden.
Biochem Biophys Res Commun. 2000 Jun 7;272(2):490-6. doi: 10.1006/bbrc.2000.2663.
VEGF is a potent angiogenic factor. We tested the hypothesis that biomechanical forces may regulate VEGF expression. By using a computerized perfusion system, human umbilical veins were exposed to high/low shear stress or intraluminal pressure (25/4 dyn/cm(2) or 40/20 mmHg) for 1.5, 3, or 6 h. Quantification of VEGF gene expression was performed with real-time RT-PCR. VEGF protein was characterized by quantitative immunohistochemistry. All perfusion experiments were performed under identical pH, PO(2), and temperature. Shear stress induced significant biphasic regulation pattern of VEGF (P = 0.0044) with significant downregulation by 45 and 40% after 1.5 and 6 h perfusion, respectively (P = 0.006 and P = 0.0002). The temporal changes of the gene expression were accompanied by synchronal changes at the protein level. High pressure induced transient 25% downregulation of VEGF gene expression after 1.5 h perfusion (P = 0.031). These data provide the first evidence on modulating effects of biomechanical forces on the vascular angiogenic property.
血管内皮生长因子（VEGF）是一种强大的血管生成因子。我们检验了生物力学力可能调节VEGF表达的假说。通过使用计算机化灌注系统，将人脐静脉暴露于高/低剪切应力或管腔内压力（25/4达因/平方厘米或40/20毫米汞柱）下1.5、3或6小时。采用实时逆转录聚合酶链反应（RT-PCR）对VEGF基因表达进行定量分析。通过定量免疫组织化学对VEGF蛋白进行鉴定。所有灌注实验均在相同的pH值、氧分压（PO₂）和温度下进行。剪切应力诱导了VEGF显著的双相调节模式（P = 0.0044），在灌注1.5小时和6小时后分别显著下调45%和40%（P = 0.006和P = 0.0002）。基因表达的时间变化伴随着蛋白质水平的同步变化。高压在灌注1.5小时后诱导VEGF基因表达短暂下调25%（P = 0.031）。这些数据首次提供了生物力学力对血管生成特性调节作用的证据。
