Rivera-Lopez Carol M, Tucker Amy L, Lynch Kevin R
Department of Pharmacology, University of Virginia, School of Medicine, Box 800735, 1340 Jefferson Park Avenue, Charlottesville, VA 22903-0735, USA.
Angiogenesis. 2008;11(3):301-10. doi: 10.1007/s10456-008-9113-5. Epub 2008 May 27.
Lysophosphatidic acid (LPA) is a simple lipid with many important biological functions such as the regulation of cellular proliferation, cellular migration, differentiation, and suppression of apoptosis. Although a direct angiogenic effect of LPA has not been reported to date, there are indications that LPA promotes angiogenesis. In addition, LPA is a chemoattractant for cultured endothelial cells and promotes barrier function in such cultures. To test the hypothesis that LPA is angiogenic, we used the chicken chorio-allantoic membrane (CAM) assay. Sequence analysis of the cloned, full-length chicken LPA receptor cDNAs revealed three receptor types that are orthologous to the mammalian LPA(1), LPA(2), and LPA(3) receptors. We document herein that LPA is angiogenic in the CAM system and further that synthetic LPA receptor agonists and antagonists mimic or block this response, respectively. Our results predict that LPA receptor antagonists are a possible therapeutic route to interdicting angiogenesis.
溶血磷脂酸（LPA）是一种简单的脂质，具有许多重要的生物学功能，如调节细胞增殖、细胞迁移、分化以及抑制细胞凋亡。尽管迄今为止尚未报道LPA有直接的血管生成作用，但有迹象表明LPA可促进血管生成。此外，LPA是培养的内皮细胞的趋化因子，并可促进此类培养物中的屏障功能。为了验证LPA具有血管生成作用这一假说，我们采用了鸡胚绒毛尿囊膜（CAM）试验。对克隆的全长鸡LPA受体cDNA进行序列分析，发现了三种与哺乳动物LPA(1)、LPA(2)和LPA(3)受体直系同源的受体类型。我们在此证明，LPA在CAM系统中具有血管生成作用，而且合成的LPA受体激动剂和拮抗剂分别模拟或阻断了这种反应。我们的结果预测，LPA受体拮抗剂可能是阻断血管生成的一种治疗途径。
