Sphingosine kinase and sphingosine 1-phosphate in cardioprotection.
Sphingosine kinase and sphingosine 1-phosphate in cardioprotection.
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DOI：
10.1097/fjc.0b013e3181926706
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发表时间：
2009-03
影响因子：
3
通讯作者：
Karliner JS
中科院分区：
文献类型：
--
作者：
Karliner JS
鞘氨醇激酶/鞘氨醇1-磷酸介导的信号转导的激活已经成为响应急性缺血/再灌注损伤的关键心脏保护途径。外源性鞘氨醇1-磷酸（S1 P）的应用在培养的心肌细胞进行缺氧或治疗的离体心脏缺血前或再灌注（药理学预处理或后处理）开始发挥促生存作用。S1 P的合成同源物模拟了这些反应。鞘氨醇激酶1同种型基因靶向小鼠无效，其心脏受到缺血/再灌注损伤，表现出梗死面积增加，对缺血预处理或缺血后处理反应不良。心脏鞘氨醇激酶活性和S1 P的测量与这些观察结果平行。高密度脂蛋白是S1 P的主要载体，对缺失S1 P受体的心脏的研究表明，高密度脂蛋白的S1 P货物具有心脏保护作用。这些观察结果对于急性和慢性心肌损伤的未来治疗方法具有相当大的相关性。
Activation of sphingosine kinase/sphingosine 1-phosphate– mediated signaling has emerged as a critical cardioprotective pathway in response to acute ischemia/reperfusion injury. Application of exogenous sphingosine 1-phosphate (S1P) in cultured cardiac myocytes subjected to hypoxia or treatment of isolated hearts either before ischemia or at the onset of reperfusion (pharmacologic preconditioning or postconditioning) exerts prosurvival effects. Synthetic congeners of S1P mimic these responses. Gene-targeted mice null for the sphingosine kinase 1 isoform whose hearts are subjected to ischemia/reperfusion injury exhibit increased infarct size and respond poorly either to ischemic preconditioning or to ischemic postconditioning. Measurements of cardiac sphingosine kinase activity and S1P parallel these observations. High-density lipoprotein is a major carrier of S1P, and studies of hearts in which selected S1P receptors have been deleted implicate the S1P cargo of high-density lipoprotein in cardioprotection. These observations have considerable relevance for future therapeutic approaches to acute and chronic myocardial injury.