Pulsatile flow-induced angiogenesis -: Role of Gi Subunits
Pulsatile flow-induced angiogenesis -: Role of Gi Subunits
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DOI：
10.1161/01.atv.0000034470.37007.58
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发表时间：
2002-10-01
影响因子：
8.7
通讯作者：
Redmond, EM
中科院分区：
文献类型：
--
作者：
Cullen, JP;Sayeed, S;Redmond, EM
目的-血管生成在正常和病理组织的生长和功能中起着关键作用。我们研究了脉动流对内皮细胞 (EC) 体外血管生成活性的影响。方法和结果 - 将牛主动脉 EC 暴露于“静态”或“流动”（1.2 至 67.0 mL/min，剪切应力 1.4 至 19.2 dyne/cm(2)）条件下 2 至 24 小时。暴露后，通过基质胶上的小管形成来测量血管生成，并通过过滤器迁移测定来评估EC迁移。脉动流以时间和力依赖性方式增加血管生成和EC迁移，在16小时时效果最大（13.2达因/cm(2)）。百日咳毒素完全抑制脉动流对血管生成和迁移的影响。用 G(i)1 或 G(i)3 α 亚基抑制性突变体（而非 G(i)2）转染 EC，分别将血流诱导的血管生成反应抑制 61 +/- 2% 和 32 +/- 6%，而用 G(i)1 或 G(i)3 α 亚基（而非 G(i)2）的组成型激活突变体转染，将血流诱导反应增加分别为 202+/-23% 和 70+/-4%。相反，通过β-肾上腺素受体激酶的羧基末端片段过度表达来抑制Goy，使血流诱导的反应增加了82+/-8%。结论-这些结果表明，脉动血流刺激血管生成，并且这种效应是由G(ialpha)1或G(ialpha)3而不是Gbetagamma亚基的激活介导的。
Objective-Angiogenesis plays a key role in the growth and function of normal and pathological tissues. We investigated the effect of pulsatile flow on endothelial cell (EC) in vitro angiogenic activity.Methods and Results-Bovine aortic ECs were exposed to "static" or "flow" (1.2 to 67.0 mL/min, shear stress 1.4 to 19.2 dyne/cm(2)) conditions for 2 to 24 hours. After exposure, angiogenesis was measured as tubule formation on Matrigel, and EC migration was assessed by filter migration assay. Pulsatile flow increased angiogenesis and EC migration in a temporal and force-dependent manner, with a maximal effect at 16 hours (13.2 dyne/cm(2)). Pertussis toxin completely inhibited the effect of pulsatile flow on angiogenesis and migration. Transfection of ECs with inhibitory mutants of the alpha subunit of G(i)1 or G(i)3, but not G(i)2, inhibited the flow-induced angiogenic response by 61 +/- 2% and 32 +/- 6%, respectively, whereas transfection with constitutively activated mutants of the a subunit of G(i)1 or G(i)3, but not G(i)2, increased the flow-induced response by 202+/-23% and 70+/-4%, respectively. In contrast, inhibition of Goy by the carboxy terminal fragment of beta-adrenergic receptor kinase overexpression increased the flow-induced response by 82+/-8%.Conclusions-These results suggest that pulsatile flow, stimulates angiogenesis and that this effect is mediated by activation of G(ialpha)1 or G(ialpha)3, but not Gbetagamma, subunits.