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Roles of prostanoids in cardiovascular system revealed from studies using knockout mice

使用基因敲除小鼠的研究揭示了前列腺素在心血管系统中的作用

基本信息

批准号：
14370049
负责人：
USHIKUBI Fumitaka
金额：
$ 9.41万
依托单位：
Asahikawa Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370049/
关键词：
prostanoid prostaglandin thromboxane 心臓血管虚血・再潅流

项目摘要

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.

前列腺素类化合物是一种脂质介质，对包括心血管系统在内的体内许多器官都有不同的影响。然而，他们在系统中的角色在很大程度上是未知的。我们试图单独使用缺乏前列腺素受体的小鼠来阐明这些作用。我们首先建立了分析的可变方法。这些包括体内模型，如压力超负荷诱导的心肌肥厚和肾血管性高血压，以及体外系统，如胚胎或成年小鼠的心肌细胞培养和肾小球旁细胞的培养。接下来，我们使用已建立的方法和基因敲除小鼠研究了前列腺素的作用。前列腺素(PG)I_2是一种通过其受体IP抑制心肌肥大和心肌纤维化的有效药物。PGI2在肾性高血压的发生发展中起着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-醛固酮系统实现的。前列腺素在心血管系统中的其他作用将在不久的将来得到阐明，因为本项目已经获得了一些有趣的结果。其中包括前列腺素在心脏缺血再灌注损伤、血管重塑和炎症性心动过速等各种病理条件下的作用。