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

点击翻译按钮获取中文摘要

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.