Nitric oxide promotes proliferation and plasminogen activator production by coronary venular endothelium through endogenous bFGF
Nitric oxide promotes proliferation and plasminogen activator production by coronary venular endothelium through endogenous bFGF
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DOI：
10.1161/01.res.80.6.845
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发表时间：
1997-06-01
影响因子：
20.1
通讯作者：
Presta, M
中科院分区：
文献类型：
--
作者：
Ziche, M;Parenti, A;Presta, M
我们以前报道过，NO是负责血管生成的内皮依赖性血管舒张肽。为了研究NO控制血管生成的机制，评估了NO影响细胞增殖和由碱性成纤维细胞生长因子（bFGF）诱导的尿激酶型纤溶酶原激活物（uPA）上调的能力，当外源性地添加到冠状静脉内皮细胞（CVEC）中或当由CVEC内源性地产生时。用NO供体硝普钠（NaNp）处理细胞诱导uPA上调和细胞增殖，这被抗bFGF抗体阻止。同样，NO依赖的促有丝分裂活性的血管舒张肽物质P（SP）被阻断的抗bFGF抗体，从而牵连内源性bFGF在NO诱导的反应。通过CVEC提取物的Western印迹分析和bFGF mRNA的差异逆转录-聚合酶链反应测定NaNp和SP诱导bFGF表达。SP诱导的bFGF上调被NO合成酶抑制剂N-ω-单甲基-L-精氨酸阻止。我们的结论是，NO通过诱导内源性bFGF促进CVECs细胞增殖和uPA上调，这一途径介导血管活性神经肽SP的血管生成反应。这种信号传导模式可能提供了一个重要的联系之间的剪切速率，NO，bFGF，和冠状动脉血管生成。
We reported previously that NO is responsible for the angiogenesis produced by endothelium-dependent vasodilating peptides. To investigate the mechanisms by which NO controls angiogenesis, NO was assessed for the ability to affect cell proliferation and upregulation of urokinase-type plasminogen activator (uPA) induced by basic fibroblast growth factor (bFGF) when added exogenously to or when produced endogenously by coronary venular endothelial cells (CVECs). The treatment of the cells with the NO donor sodium nitroprusside (NaNp) induced uPA upregulation and cell proliferation, which were prevented by anti-bFGF antibodies. Similarly, the NO-dependent mitogenic activity of the vasodilating peptide substance P (SP) was blocked by anti-bFGF antibodies, thus implicating endogenous bFGF in the NO-induced response. NaNp and SP induced bFGF expression as measured by Western blot analysis of CVEC extracts and by differential reverse transcriptase-polymerase chain reaction of bFGF mRNA. SP-induced upregulation of bFGF was prevented by the NO synthase inhibitor N-omega-monomethyl-L-arginine. We conclude that NO promotes cell proliferation and uPA upregulation in CVECs by inducing endogenous bFGF and that this pathway mediates the angiogenetic response to the vasoactive neuropeptide SP. This signaling paradigm may provide an important link between shear rate, NO, bFGF, and coronary angiogenesis.