Sphingosine-1-phosphate receptor 3 promotes neointimal hyperplasia in mouse iliac-femoral arteries.
Sphingosine-1-phosphate receptor 3 promotes neointimal hyperplasia in mouse iliac-femoral arteries.
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DOI：
10.1161/atvbaha.111.241034
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发表时间：
2012-04
期刊：
影响因子：
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通讯作者：
Daum G
中科院分区：
文献类型：
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作者：
Shimizu T;De Wispelaere A;Winkler M;D'Souza T;Caylor J;Chen L;Dastvan F;Deou J;Cho A;Larena-Avellaneda A;Reidy M;Daum G
本研究的目的是确定S1 PR 3在内膜增生中的作用。野生型和S1 PR 3缺失小鼠的髂股动脉剥脱模型用于定义S1 PR 3在动脉损伤反应中的作用，因为我们在人类和小鼠中发现，与颈动脉相比，S1 PR 3在这些动脉中的表达更高。在手术后28天，野生型动脉形成的病变明显大于S1 PR 3无效动脉。BrdU标记实验表明，在损伤时，野生型动脉表现出比S1 PR 3-null动脉更高的中膜和内膜增殖。由于S1 PR 3在体外表达较低，我们使用逆转录病毒介导的基因转移在S1 PR 3缺失的SMC中表达S1 PR 3，以研究S1 PR 3对细胞功能和信号传导的影响。表达S1 PR 3的SMC，而不是载体转染的对照，响应于S1 P刺激，激活Rac，Erk和Akt。表达S1 PR 3的SMC也生长迁移更多。在人类和小鼠中，与颈动脉相比，S1 PR 3在髂股动脉中的表达更高。S1 PR 3促进小鼠髂股动脉剥脱后的新生内膜增生，可能是通过激活涉及Erk、Akt和Rac的信号通路刺激细胞迁移和增殖。
The objective of this study is to define a role for S1PR3 in intimal hyperplasia. A denudation model of the iliac-femoral artery in wild-type and S1PR3-null mice was used to define a role for S1PR3 in the arterial injury response because we found in humans and mice that expression of S1PR3 is higher in these arteries when compared to carotid arteries. At 28 days after surgery, wild-type arteries form significantly larger lesions than S1PR3-null arteries. BrdU labeling experiments demonstrate that upon injury, wild-type arteries exhibit higher medial as well as intimal proliferation than S1PR3-null arteries. Because S1PR3 expression in vitro is low, we expressed S1PR3 in S1PR3-null SMCs using retroviral-mediated gene transfer to study S1PR3 effects on cell functions and signaling. SMCs expressing S1PR3, but not vector-transfected controls, respond to S1P stimulation with activation of Rac, Erk and Akt. SMCs expressing S1PR3 also grow migrate more. In humans and mice, S1PR3 expression is higher in iliac-femoral arteries compared to carotid arteries. S1PR3 promotes neointimal hyperplasia upon denudation of iliac-femoral arteries in mice, likely by stimulating cell migration and proliferation through activation of signaling pathways involving Erk, Akt and Rac.