Roles of prostanoids in cardiovascularsystem revealed from studies using knockout mice

前列腺素类是脂质介质，对身体的许多器官（包括心血管系统）显示可变的影响。然而，他们在系统中的作用在很大程度上是未知的。我们试图用缺乏前列腺素受体的小鼠来阐明这些作用。我们首先建立了变量分析方法。这些包括体内模型，例如心脏肥大、血栓栓塞、血管重塑和肾血管性高血压，以及用于培养血管平滑肌细胞、培养来自胎儿或成年小鼠的心肌细胞、血小板聚集和血管张力的体外系统。我们用建立的方法和基因敲除小鼠研究了前列腺素的作用，发现前列腺素（PG）1_2是一种有效的保护心肌细胞免受缺血-再灌注损伤的介质。PGE_2可增强血栓素A_2和ADP等血小板刺激剂诱导的血小板活化作用。此外，这种对血小板的增强作用被证实在止血和血栓栓塞中都是重要的。前列腺素类在心血管系统中的其他作用将在不久的将来得到澄清，因为在本项目中已经获得了一些有趣的结果。它们包括在各种病理条件下的作用，如心脏肥大，血管重塑和肾血管性高血压

The prostanoids are lipid mediators showing variable effects on many organs in the body including the cardiovascular system. Their roles in the system, however, have been largely unknown. We attempted to clarify these roles using mice lacking the prostanoids receptors individually. We first established variable methods for the analysis. These include in vivo models such as for cardiac hypertrophy, thromboembolism, vascular remodeling and renovascular hypertension, and in vitro systems for culture of vascular smooth muscle cells, cultures of cardiomyocytes from fetal or adult mice, platelet aggregation and vascular tone. We next examined the roles of the prostanoids using the established methods and knockout mice, Prostaglandin (PG)l_2 was found to be a potent mediator to protect the cardiomyocytes from ischemia-reperfusion injury. PGE_2 potentiated the platelet activation induced by other platelet stimulants, such as thromboxane A_2 and ADP. Furthermore, this potentiating effect on the platelets was verified to be important in both hemostasis and thromboembolism. Other roles of the prostanoids in the cardiovascular system would be clarified in near future, because several interesting results have been already obtained in the present project. They include the roles in various pathological conditions such as cardiac hypertrophy, vascular remodeling and renovascular hypertension