Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI 53226, USA.
Front Biosci (Landmark Ed). 2013 Jun 1;18(3):852-61. doi: 10.2741/4148.
Lysophosphatidic acid (LPA) as a bioactive phospholipid signaling mediator is emerging as an important regulator of endothelial cell functions and angiogenesis. Many studies have shown that LPA is an active player in regulating the processes of endothelial cell migration, proliferation, and differentiation, all essential in angiogenesis. Through modulating angiogenesis associated gene expression, LPA also promotes pathological angiogenesis. Intriguingly, the angiogenic signaling mechanisms mediated by LPA have been linked to specific G-protein coupled receptors and down stream MAPK including Erk1/2, p38 and JNK, protein kinase D (PKD-1), Rho kinase (ROCK), and the NF-kappa B signaling pathways. LPA regulates angiogenic responses via a complex signaling network, and LPA signaling is integrated and transduced to the nucleus to coordinate the transcription of different angiogenic genes. Investigation of these mechanisms will provide novel and valuable insights into the understanding of endothelial cell biology and angiogenic programs. This knowledge will facilitate designs for better therapies for the ischemic cardiovascular diseases and malignant tumors.
溶血磷脂酸（LPA）作为一种生物活性磷脂信号介质，正在成为内皮细胞功能和血管生成的重要调节剂。许多研究表明，LPA 是调节内皮细胞迁移、增殖和分化过程的活跃因子，这些过程对于血管生成都是必不可少的。通过调节与血管生成相关的基因表达，LPA 也促进病理性血管生成。有趣的是，LPA 介导的血管生成信号机制与特定的 G 蛋白偶联受体和下游 MAPK 包括 Erk1/2、p38 和 JNK、蛋白激酶 D（PKD-1）、Rho 激酶（ROCK）和 NF-κB 信号通路有关。LPA 通过复杂的信号网络调节血管生成反应，LPA 信号被整合并转导到核内，以协调不同血管生成基因的转录。对这些机制的研究将为理解内皮细胞生物学和血管生成程序提供新的有价值的见解。这些知识将有助于为缺血性心血管疾病和恶性肿瘤设计更好的治疗方法。
