Roles of prostanoids in cardiovascularsystem 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

• 批准号: 11470020
• 负责人: USHIKUBI Fumitaka
• 金额: $ 9.34万
• 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: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470020/
• 关键词: prostanoids; prostaglandin; thromboxane; knockout mice; prostanoid receptor; cardiovascular system; platelets; ischemia-reperfusion; 循環器; 心筋虚血; 心肥大; prostanoids; prostaglandin; thromboxane; knockout mice; prostanoid receptor; cardiovascular system; platelets; ischemia-reperfusion; 循環器; 心筋虚血; 心肥大

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

前列腺素是脂质介质，显示对体内许多器官（包括心血管系统）的影响。但是，它们在系统中的作用在很大程度上是未知的。我们尝试使用缺乏前列腺素受体的小鼠来阐明这些角色。我们首先建立了用于分析的变量方法。这些包括体内模型，例如心脏肥大，血栓栓塞，血管重塑和肾血管高血压，以及用于血管平滑肌细胞培养的体外系统，胎儿或成人小鼠的心肌细胞培养物，血小板聚集和血管张力。接下来，我们使用已建立的方法和基因敲除小鼠检查了前列腺素的作用，前列腺素（PG）L_2被认为是保护心肌细胞免受缺血再灌注损伤的有效介质。 PGE_2增强了由其他血小板刺激剂（例如Thromboxane A_2和ADP）诱导的血小板激活。此外，这种对血小板的增强作用在止血和血栓栓塞中都很重要。前列腺素在心血管系统中的其他作用将在不久的将来阐明，因为本项目已经获得了一些有趣的结果。它们包括在各种病理状况中的作用，例如心脏肥大，血管重塑和肾血管高血压