Roles of prostanoids in cardiovascular system 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，例如压力超负荷诱导的心脏肥大和肾血管性高血压，以及体外系统，例如来自胎儿或成年小鼠的心肌细胞的培养物和肾上腺髓质细胞的培养物。接下来，我们使用已建立的方法和敲除小鼠检查了前列腺素类的作用。前列腺素（PG）I_2通过其受体IP抑制心肌肥大和心肌纤维化。PGI_2在肾血管性高血压的发生发展中起重要的病理生理作用。这一作用是通过PGI_2刺激肾素-血管紧张素-醛固酮系统而实现的。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。它们包括前列腺素类在各种病理条件下的作用，如心脏缺血-再灌注损伤、血管重塑和炎性心动过速。

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 attmpted 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 pressure overload-induced cardiac hypertrophy and renovascular hypertention, and in vitro systems such as for cultures of cardiomyocytes from fetal or adult mice and culture of juxtagromerullar cells. We next examined the roles of the prostanoids using the established methods and knockout mice. Prostaglandin (PG) I_2 was found to be a potent inhibitor of cardiac hypertrophy consisting of cardiomyocyte hypertrophy and cardiac fibrosis via its receptor IP. PGI_2 playd an important pathophysiological role in the development of renovascular hypertension. This role was attained by the stimulation of the renin-angiotensine-aldosterone system by PGI_2. 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 of the prostanoids in various pathological conditions such as cardiac ischemia-reperfusion injury, vascular remodeling and inflammatory tachycardia.