Sphingosine kinase modulates microvascular tone and myogenic responses through activation of RhoA/Rho kinase
Sphingosine kinase modulates microvascular tone and myogenic responses through activation of RhoA/Rho kinase
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DOI：
10.1161/01.cir.0000080324.12530.0d
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发表时间：
2003-07-22
期刊：
影响因子：
37.8
通讯作者：
Pohl, U
中科院分区：
文献类型：
--
作者：
Bolz, SS;Vogel, L;Pohl, U
背景：rhoa和Rho激酶是微血管张力的重要调节剂。方法和结果：我们测试了产生内源性鞘脂介质鞘鞘醇-1-磷酸（S1P）的鞘鞘醇激酶（Sphk1）是否参与激活RhoA/Rho激酶途径的信号级联反应。利用一种新的转染模型，我们报道了分离的阻力动脉的静息张力和肌生成反应随着Sphk1在这些动脉平滑肌细胞中的强制表达而增加。Sphk1显性阴性突变体过表达或RhoA或Rho激酶显性阴性突变体与Sphk1共同表达完全抑制张力和肌原性反应的发展。结论Sphk1过表达的调高作用提示Sphk1可能在外周抵抗的控制中起重要作用。
Background-RhoA and Rho kinase are important modulators of microvascular tone.Methods and Results-We tested whether sphingosine kinase (Sphk1) that generates the endogenous sphingolipid mediator sphingosine-1-phosphate (S1P) is part of a signaling cascade to activate the RhoA/Rho kinase pathway. Using a new transfection model, we report that resting tone and myogenic responses of isolated resistance arteries increased with forced expression of Sphk1 in smooth muscle cells of these arteries. Overexpression of a dominant negative Sphk1 mutant or coexpression of dominant negative mutants of RhoA or Rho kinase together with Sphk1 completely inhibited development of tone and myogenic responses.Conclusions-The tone-increasing effects of a Sphk1 overexpression suggest that Sphk1 may play an important role in the control of peripheral resistance.