1：溶血磷脂酸受体及下游信号通路在心脏细胞生长中的调节作用.pdf

生理学报 Acta Physiologica Sinica, October 25, 2007, 59 (5): 619-627 619 综 述 溶血磷脂酸受体及下游信号通路在心脏细胞生长中的调节作用 陈 曦* 中国医学科学院/ 中国协和医科大学心血管病研究所，阜外心血管病医院，北京 100037 摘 要：溶血磷脂酸(lysophosphatidic acid, LPA) 是一种十分活跃的磷脂信号分子，具有广泛的生物学效应，包括诱导神 经轴突回缩、应力纤维形成、促进血小板凝集、诱导平滑肌收缩、刺激血管平滑肌细胞增殖等。LP A 通过其受体及耦 联的G 蛋白调节细胞内信号途径，介导各种生物学效应。心脏组织中存在多种LPA 受体亚型，尤其受体LPA1 亚型在心 脏组织中的含量仅次于脑，位居第二，暗示LPA 在心脏中有重要的生物学功能。本文着重对LPA 的5 种受体亚型的组织 分布、与G 蛋白的耦联和对第二信使的活性调节，以及LPA 及其受体亚型对心脏细胞的生长调节作一综述。 关键词：溶血磷脂酸受体；心脏；细胞增殖；肥大；凋亡 中图分类号：R331.3 + 1 ；Q2 57 Lysophosphatidic acid receptors and the downstream signaling pathways in regulation of cardiac cell growth CHEN Xi* Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China Abstract: Lysophosphatidic acid (LPA) is a bioactive phospholipid messenger with multiple biological functions, including induction of neurite retraction, stress fiber formation, promotion of platelet aggregation and stimulation of smooth muscle contraction and cell proliferation. LPA exerts various biological functions through G protein-coupled receptors and the downstream cellular signaling pathways. LPA and its receptors may also play important roles in the heart since several LPA receptor subtypes exist in the heart and especially the level of LPA1 subtype is the second highest, just lower than that in the brain. The review was focused on 5 subtypes of LPA receptor, mainly on their tissue expression pattern, coupled G proteins and signal pathways, as well as the roles of LPA and its receptors in regulation of cardiac cell growth. Key words: lysophosphatidic acid receptors; heart; cell proliferation; hypertrophy; apoptosis 溶血磷脂酸(lysophosphatidic acid, LPA)是一种 增殖/ 凋亡、血小板聚集、肿瘤细胞浸润等。 LPA 结构最简单的水溶性甘油磷脂，其化学结构名称为 可以引起多种血管反应，如激活血小板、促进血管 1- 酰基-2- 羟基-3- 磷酸甘油 (1-acyl-2-hydroxy-sn - 平滑肌收缩和细胞增殖、活化内皮细胞，与高血 glycerol-3-phosphate) 。以往认为L